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2013 Veterinary Developmental Anatomy (Veterinary Embryology) CVM 6903 by Thomas F. Fletcher, DVM, PhD and Alvin F. Weber, DVM, PhD 1  CONTENTS Early...

2013 Veterinary Developmental Anatomy (Veterinary Embryology) CVM 6903 by Thomas F. Fletcher, DVM, PhD and Alvin F. Weber, DVM, PhD 1  CONTENTS Early Embryogenesis......................................................3 Musculo-Skeletal Development....................................16 Serous Body Cavities.....................................................23 Cardiovascular System.................................................25 Digestive System............................................................32 Respiratory System.......................................................38 Urinary System..............................................................41 Genital System...............................................................44 Pharynx, Face, Nasal Cavity & Mouth......................49 Nervous System & Special Senses................................56 Appendix I. Gametogenesis..........................................69 Appendix II. Mitosis and Meiosis................................71 Appendix III. List of Anomalies...................................75 2  Early Embryogenesis Embryogenesis: — formation of body structures & organs (organogenesis) — requires cell division (proliferation) and cell differentiation (specialization) — produces the great variety of cell types and extracellular products found in the body. Cell specialization: — selective gene expression (and resultant protein production) is the ultimate explanation for the cell differentiation process during embryogenesis. — genetic expression by a particular cell depends on the cell’s previous genetic history (com- mitment lineage) and its current cellular environment (intercellular communications). Cell Differentiation stem cell committed cells specialized cell pyramidal neuron e.g., neuroblast ectoderm neural epithelium stellate neuron, etc. astrocyte glioblast oligodendrocyte Cell differentiation is the result of cells expressing some genes and suppressing others within a common genome. Cells differ because they produced different proteins/peptides. Proteins & peptides are: — structural components (cytoskeleton or extracellular structures) — enzymes (controlling cell metabolism) — secretory products (e.g., hormones; digestive enzymes; etc.) — channels & pumps (passage of molecules across membranes) — receptors (communication, etc.) Periods: Embryonic Period — defined as the time from fertilization to the earliest (primordial) stages of organ development (about 30 days in dog, cat, sheep, pig; almost 60 days in horse, cattle, human). Fetal Period — the time between the embryonic period and parturition (the end of gesta- tion), during which organs grow and begin to function. Fertilization: — union of a haploid oocyte and a haploid spermatozoon, producing a diploid zygote (a pleuripotent cell capable of developing into a new individual) — fertilization begins with gamete fusion (zygote formation) — fertilization ends with the initiation of zygote cell division (the start of cleavage) Fertilization related details: — fusion of a spermatozoon with an oocyte takes place in the uterine tube, near the ovary — the spermatozoon must bind to a specific glycoprotein on the zona pellucida surrounding the oocyte [this species recognition process prevents union with foreign sperm]; 3  — then the spermatozoon releases degradative enzymes (acrosomal reaction) [the enzymes denature the zona pellucida, allowing the sperm cell to penetrate the barrier] — spermatozoon and oocyte plasma membranes fuse (secondary oocyte completes meiosis) — the oocyte immediately cancels its membrane potential (via Ca++ influx) and then denatures its zona pellucida (via enzymes are released by exocytosis from oocyte cytoplasmic granules) [this prevents fusion by additional sperm] — male & female haploid pronuclei make contact, lose their nuclear membranes, and begin mitosis (mitosis begins 12 hours after sperm fusion; DNA synthesis takes place before mitosis) Oocyte (enveloped by a zona pellucida (glycoprotein membrane) and corona radiata (granulosa cells) at ovulation) — selective follicles mature at each cycle (in response to circulating FSH hormone from the pituitary) — oogonia (germ cells) give rise to primary oocytes by mitosis within the embryo — primary oocytes initiate Meiosis I (reduction division) within the embryo and only resume Meiosis I following ovulation (being suspended in Meiosis I by inhibitory secretion of follicle granulosa cells) — secondary oocytes complete meiosis (Meiosis II) following fertilization (if unfertilized they degenerate), producing a fertilized oocyte (ovum). Spermatozoa (several hundred million per ejaculate) — propelled from vagina to uterine tube by contraction of female genital tract — spermatogonia (germ cells) give rise to primary spermatocytes by mitosis repetitively following puberty — primary spermatocytes undergo Meiosis I (reduction division) producing secondary spermatocytes — secondary spermatocytes complete meiosis (Meiosis II), producing spermatids that undergo transformation into spermatozoa (spermiogenesis) — subsequently, spermatozoa undergo capacitation (removal of surface proteins that would impede contact with an oocyte) Cleavage: — refers to the initial series of mitotic divisions by which the large zygote is fractionated into numerous “normal size” cells. — each daughter cell of the cleavage process is termed a blastomere. — cleavage begins with a zygote, progresses through compaction to a morula stage and terminates at the start of the blastocyst (blastula) stage — the first eight blastomeres are undifferentiated and have identical potential in mammals; thereafter, blastomeres differentiate into inner & outer cells with different missions First Second Cleavage Cleavage Blastula Division Division Morula (Blastocyst) inner outer cell zona blastomeres mass pellucida blastocoele blastomeres inner blastomeres trophoblasts Note: The first cleavage division occurs 1 to 5 days following ovulation (depending on species), thereafter cells divide about once every 12 hours; As many as eight generations of mitoses may occur without intervening cell growth (cytoplasmic increase). Thus, e.g., one 150 micron diameter zygote can becomes a collection of 256 cells, each about 7 microns in diameter. 4 Morula [L.= small mulberry] — a solid ball of blastomeres within a zona pellucida (typically consisting of 16 to 64 blastomeres) — blastomeres become compacted; cells on the inside differentiate from those along the surface of the morula: — outer blastomeres become flattened and form tight junctions (reducing fluid permeability); they develop the capacity to secrete fluid (internally); they are destined to become trophoblasts which form the chorion & amnion (fetal membranes) of the conceptus; — inner blastomeres form gap junctions to maximize intercellular communication; they are destined to become inner cell mass which forms the embryo itself (plus two fetal membranes). Note: As few as three inner blastomeres are sufficient to produce an entire embryo (and adult). When a morula leaves the uterine tube and enters the uterus (uterine horn) it is at about the 16-cell stage, around 4 to 7 days after fertilization (depending on species). The 32-cell stage morula (5-7 days post ovulation) is ideal for embryo transfer in cattle. Blastocyst (or Blastula) — develops during the second week, after the zona pellucida ruptures — consists of a large number of blastomeres arranged to form a hollow, fluid-filled, spherical or cylindrical structure — contains an inner cell mass (embryoblast), evident as a collection of cells localized inside one polar end of the blastula — surface cells of the blastocyst are designated trophoblasts (future chorion of the conceptus) — the cavity of the blastocyst is called a blastocoele — eventually the blastocyst attaches to or implants within the uterine wall (pending species). Cleavage in fish, reptiles, and birds: Large quantities of yolk impede cell division during cleavage. Thus a blastodisc (rather than a spherical or elliptical blastocyst) is formed at the animal pole of the egg. A telolecithal ovum (egg with large amounts of asymmetrically distributed yolk) has an animal pole where the nucleus is located and an opposite vegetal pole where yolk is concentrated. Cleavage is par- tial (meroblastic): cells divide more rapidly at the animal pole than at the vegetal pole, resulting in many, small blastomeres at the animal pole and a few, large macromeres at the vegetal pole. In contrast, mammalian ovum has meager amounts of yolk (oligolecithal ovum) which is uni- formly distributed (isolecithal). Cleavage is holoblastic (total) and each blastomere division produces two equal-size daughter cells. Thus animal and vegetal poles are not evident in mammalian ova. TWINS Monozygotic: identical (same genetic composition) twins can result from either: 1] separation of early blastomeres (up to the 8-cell stage)—each of the separate blastomere(s) develops into an independent conceptus; or 2] separation of inner blastomeres within a single morula—each of the separate blastomere(s) develops into an independent embryo and both embryos share a common placenta (this is less common than the first possibility). Note: Separations later in embryonic development result in conjoined twins (diplopagus; Siamese twins), or double heads, etc. types of anomalies. Dizygotic: fraternal twins result when two zygotes develop “independently” during the same pregnancy (independence can be compromised by fusion of fetal membranes and blood supplies). It is possible for fraternal blastomeres to merge and produce a single conceptus with two different genotypes (a chimera). 5  GERM LAYERS Ectoderm, mesoderm and endoderm are designated primary germ layers because origins of all organs can be traced back to these three layers. Ectoderm forms epidermis of the skin, epithelium of the oral and nasal cavities, and the nervous system and sense organs. Mesoderm forms muscle and connective tissue, including bone, and components of the circulatory, urinary and genital systems. Endoderm forms mucosal epithelium and glands of respiratory and digestive systems. Gastrulation: The morphogenic process that gives rise to three germ layers: ectoderm, mesoderm, and endoderm. (In some species, evidence of primitive gut formation can be seen [gastrula Gr.= little stomach].) Gastrulation includes the following sequence, beginning with a blastocyst: — A thickened embryonic disc becomes evident at the blastocyst surface, due to cell prolifera- tion of the inner cell mass cells. Trophoblast cells overlaying the inner cell mass degenerate in domestic mammals (in the mouse and human, trophoblast cells overlaying the inner cell mass separate and, instead of degenerating, become amnionic wall.) — From the inner cell mass, cells proliferate, break loose (delaminate), and migrate to form a new cell layer inside the trophoblast layer. The new layer of cells, called the hypoblast, will form a yolk sac. The remaining inner cell mass may be called the epiblast. — On the epiblast surface, a primitive streak forms as differential cell growth generates a pair of ridges separated by a depression. [NOTE: The primitive streak defines the longitudinal axis of the embryo and indicates the start of germ layer formation.] Hypoblast Formation (three stages) embryonic disc embryonic disc magnified degenerating trophoblast blastocoele inner cell mass delaminating trophoblast hypoblast cells layer hypoblast layer epiblast epiblast coelom trophoblast layer yolk sac (primitive gut) coelom hypoblast layer yolk sac (primitive gut) 6 — Deep to the primitive streak, a Dorsal View of Embryonic Disc space (coelom/celom) becomes evident between the hypoblast notochord layer and epiblast. Subsequently, the coelom is filled by mesoderm that undergoes cavitation and primitive gives rise to body cavities. node — Epiblast cells proliferate along primitive primitive streak margins and mi- streak grate through the streak into the coelom. The migrating cells form primary mesenchyme endoderm & mesoderm layers. — Initial migrating cells join the NOTE: Arrows indicate the spread of primary hypoblast layer, forming embry- mesenchyme through the primitive streak onic endoderm (hypoblast cells and between the epiblast and hypoblast constitutes yolk sac endoderm). — The majority of migrating cells enter the coelom as primary mesenchyme and become meso- derm. The primary mesenchyme migrates laterally and cranially (but not along the midline region directly cranial to the primitive streak where notochord will form). Note: Mesoderm divides into: paraxial, intermediate, and lateral mesodermal regions. primitive streak epiblast (ectoderm) hypoblast endoderm primary mesenchyme (mesoderm) — Within the lateral mesoderm, cavitation re-establishes a coelom (hoseshoe-shaped). The mesoderm splits into two layers bordering the coelom—somatic mesoderm is attached to the ectoderm and splanchnic mesoderm is joined to endoderm. — The remaining epiblast becomes ectoderm which forms skin epidermis & nervous system. 7  NOTE: Mesoderm can exist in two morphologic forms: mesenchyme and epithelioid: Mesenchyme features aggregates of stellate cells within an abundant extracel- lular matrix composed of fluid and macromolecules (polymers). Epithelioid refers to organized cells having distinct apical and basal surfaces; the latter commonly rests on a basal lamina produced by epithelioid secretion. Mesoderm can transform from a mesenchyme to epithelioid and vice versa: The mesoderm that streams through the primitive streak is primary mesenchyme. Somatic, splanchnic, and somite mesoderm can be temporarily epithelioid. The temporary epithelioid transforms to a secondary mesenchyme which ulti- mately forms muscle and connective tissue (including cartilage, bone, liga- ments, tendons, dermis, fascia, and adipose tissue). Thus, the term “mesenchyme” refers to the morphologic appearance of embryonic tis- sue. Although most mesenchyme is mesoderm, the other germ layers can also form mesenchyme, e.g., ectomesenchyme from neural crest ectoderm. Formation of the Notochord: The notochord is a rod-shaped aggregate of cells located between ectoderm and endoderm anterior to the primitive streak of the embryo. It occupies the midline coelomic space that was not invaded by migrating primary mesenchyme. The notochord is important because it induces: formation of the head process, development of the nervous system, and formation of somites The notochord marks the future location of the vertebral column and the base of the cranium. The ultimate fate of the notochord is to become nucleus pulposus of intervertebral discs. Note: The notochord develops from the primitive node located at the cranial end of the primitive streak. From the node, mesoderm-forming cells proliferate and migrate forward into the future head region where they become the rod-shaped notochord. 8  Note: Each organ system has a critical period during development when it is most sensitive to external agents (teratogens) that produce birth defects. Early Formation of the Nervous System (Neurulation): Neurulation refers to notochord-induced transformation of ectoderm into nervous tissue. The process begins during the third week in the region of the future brain and then progresses caudally into the region of the future spinal cord. The neurulation process involves the following steps: — ectodermal cells overlaying the notochord become tall columnar Neurulation (neuroectoderm); they form a paraxial mesoderm neuroectoderm intermediate mesoderm thickened area designated the neural plate. The other ectodermal epithelium is flattened. lateral mesoderm — a neural groove is formed as somatic notochord splanchnic edges of the neural plate be- endoderm come raised on each side of a neural groove coelom midline depression. (Apical ends ectoderm of individual neuroectodermal cells constrict.) somite — a neural tube is then formed as the neural groove undergoes midline merger of its dorsal edges. The tube separates from neural tube neural crest non-neural ectoderm which unites dorsal to it. (Tube formation begins in the cranial cervical region of the central nervous system and progresses cranially and caudally until anterior and posterior neuropores, the last openings, finally close.) — bilaterally, where the neural groove is joined to non-neural ectoderm, cells detach as the neural groove closes; the cells proliferate and assume a position dorsolateral to the neural tube—forming neural crest. NOTE: Neural tube becomes the central nervous system, i.e., the brain and spinal cord. Neural crest cells are remarkable for the range of structures they form. Some cells mi- grate dorsally and become pigment cells in skin. Other cells migrate ventrally and be- come neurons and glial cells of the peripheral nervous system, or adrenal medulla cells. In the head, neural crest forms mesenchyme (ectomesenchyme) which becomes menin- ges, bone, fascia, and teeth. 9 Somites: Mesoderm blocks located just lateral to the notochord, which induced somite development. A pair of somites develops for every vertebra, plus a half dozen somite pairs in the head. Number of somites in an embryo is indicative of age, individual somites develop chronologically, in craniocaudal order. Somites develop as follows: — mesoderm, designated paraxial mesoderm, accumulates on each side of the notochord — progressing from rostral to caudal over time, transverse fissures divide the paraxial mesoderm into blocks — each block becomes a somite (epithelioid cells within a somite block re-orient 90°, from transverse to the notochord to longitudinal) otic placode — head (occipital) somites develop from proliferation of local mes- enchyme lateral to the cranial end of the notochord — rostral to the notochord, mes- optic enchyme forms less-developed placode somites, called somitomeres; these migrate into pharyngeal pharyngeal arches and form muscles of the arches jaw, face, pharynx, & larynx. heart NOTE: umbilical Each somite differentiates into three stalk regions: Sclerotome (ventromedial region) gives rise to vertebrae, ribs, and endochondral bones at the base of the skull. Dermatome (lateral region) gives rise to the dermis of skin somites Myotome (intermediate region) gives rise to skeletal muscles of the body 10 Development of a Cylindrical Body: The early embryo is flat, but the vertebrate body plan features a cylindrical theme—various cylindrical structures (derivatives of the gut, neural tube, notochord, etc.) enclosed within a cylindri- cal body. Transition from a flat embryo to a cylindrical one involves the following developments: Head Process Formation: Three Stages of The cranial end of the embryo grows dorsal- Head Process Formation ly and forward so that it projects above the region (longitudinal views) originally in front of the embryo. The cylindrical head process elongates by ectoderm additional growth from its base (located in front mesoderm of the primitive node). Consequently, the most anterior endoderm part of the embryo is the oldest. The elongation incorporates yolk sac the most anterior half-dozen somites into the future head. Within the head process, endoderm is reflect- ed ventrally upon itself, forming a blind-ended head foregut (future pharynx). process Tail Fold Formation: At the caudal end of the embryo, a cylindrical tail fold is formed in a manner similar oral plate to that of the head process. Folded endoderm encloses a blind hindgut. Lateral Body Folds: head As the head process elongates upward & process forward, a subcephalic pocket (space) is formed ventral to the head process, between the head subcephalic process and extra-embryonic tissue. The bilateral pocket margins of this pocket are lateral body folds— pharynx which constitute the Dorsal View elevated continuity between head the elevated embryo process and the relatively flat extra-embryonic lateral body tissue. yolk sac pericardium fold Similar folds exist caudally in association with the tail process. As the embryo grows and is elevated dorsally, lateral body folds ad- primitive duct and join together ventrally, establishing a tubular embryo sepa- node rated from flattened extra-embryonic tissue. primitive Progressing caudally from the head process and cranially from the streak tail fold, ventral fusion of lateral body folds stops at the umbilicus— leaving a ventral opening in the body wall that allows vessels and the yolk sac and allantois to enter the embryo (and communicate with the gut). 11  Ventral fusion of lateral body folds Mesoderm distinguishes the embryo from extra-em- = somite neural tube bryonic tissue (fetal membranes): = intermediate notochord — embryonic coelom (future body = lateral foregut cavities of the trunk) is distinguished from Lateral extra-embryonic coelom within fetal mem- Body branes. Folds — somatopleure (somatic mesoderm + embryonic coelom ectoderm) that forms body wall is distin- mesentery guished from that forming fetal membranes (chorion and amnion). — splanchnopleure (splanchnic me- soderm + endoderm) merges bilaterally to somatopleure extra-embryonic splanchnopleure yolk coelom form gut and mesentery, differentiated from sac extra-embryonic yolk sac (and allantois). Pharyngeal Arches: In the head region, dorso-ventral arches demarcated by grooves (clefts) appear. The arches are called pharyngeal arches and they are bounded internally by pharyngeal pouches. Each arch contains a vessel (aortic arch). Within each arch, ectomes- enchyme (derived from neural crest) gives rise to bone and fascia. Myotomes of somitomeres migrate to pharyngeal arches to provide skeletal musculature. Each arch is innervated by one cranial nerve. Only the first three pharyngeal arches are externally evi- dent in mammals. The first arch develops into upper and lower jaws and muscles of mastication. The second gives rise to hyoid bones and muscles of the face. The remaining pharyngeal arches form hyoid bones, larynx and associated muscles. Each arch is innervated by a particular cranial nerve. The pharynx (foregut) develops five bilateral diverticula that internally demarcate the pharyn- geal arches. These pharyngeal pouches develop into auditory tube, parathyroid glands, thymus, etc. NOTE: In fish, five or six branchial [Gr. = gill] arches are well developed. Cells degenerate where branchial clefts and pharyngeal pouches meet so that the pharynx communicates with the outside (this occurs only temporarily between the first two arches in mammals). The first arch forms the jaw apparatus and the rest form gill arches separated by gill slits. 12 Flexures: The tube-shaped embryo undergoes three flexures that make it C-shaped. The first occurs in the future midbrain region, the second in the future neck region, and the third occurs in the tail region. Cardiovascular system: The cardiovascular system develops early (in the third week after the start of the nervous system), as the embryo enlarges and diffusion alone becomes inadequate for tissue preservation. Angiogenesis (formation of blood vessels) begins in splanchnic mesoderm of the yolk sac, in the form of blood islands composed of mesenchyme and hemocytoblasts. The latter forms blood cells and the mesenchyme forms vesicles lined by endothelium. The vesicles coalesce to form vascu- lar channels and then blood vessels (the latter are formed by budding, fusion, & enlargement). Vessels are formed first in extra-embryonic tissue: vitelline (yolk sac) and umbilical (allan- toic) vessels appear first. Ventral to the pharynx, bilateral vessels merge to form a tubular heart; dorsal and ventral aortae are connected by aortic arches. Also, cranial and caudal cardinal veins return embryonic blood to the heart and umbilical veins return placental blood to the heart. None of these vessels will persist as such in the adult. Placentation Placenta = region(s) of apposition between uterine lining and fetal membranes where metabolites are exchanged for sustaining pregnancy. Chorion forms the surface fetal membrane. Apposition areas (placental types) may be: dif- fuse (pig), zonary (carnivore), discoid (primates & rodents), or involve placentomes. A placentome is a discrete area of interdigitation between a maternal caruncle and a fetal cotyledon. Equine placentas are microcotyledonary (microplacentomes are distributed diffusely). Ruminant placentas consist of rows of relatively large placentomes. Placentas (placentae) may also be classified according to the tissue layers separating fetal and maternal blood. Uterine epithelium, uterine connective tissue and uterine endothelium may be eroded, giving rise to four placental types: epitheliochorial (swine, equine, cattle); synepitheliochorial, formerly called syndesmochorial, (sheep, goats); endothelial chorial (carnivore); and hemochorial (primates & rodents). 13  Fetal Components of Placentae Porcine Chorionic Surface (folds; diffuse placental contact) (chorion without allantois) necrotic tip cervical star (region over cervix) Equine Chorionic Surface (microcotyledons) Bovine Chorionic Surface (rows of cotyledons) Carnivore Chorionic Surface (zonary placental contact) Human/Rodent Chorionic Surface (discoid placental contact) marginal hematoma marginal hematoma 14 Fetal membranes: Four fetal membranes develop in a conceptus. Two arise from the trophoblast layer of the blastocyst (and are continuous with the somatopleure of the embryo). Two arise from the inner cell mass of the blastocyst (and are continuous with splanchnopleure of the embryo); these two splanch- nopleure membranes are vascular. The four fetal membranes are: chorion allantois embryo amnion somatopleure coelom gut splanchnopleure yolk sac 1. Chorion — forms the outer boundary of the entire conceptus (from trophoblast) 2. Amnion — encloses the embryo within a fluid-filled amnionic cavity; formed by folds of chorion in domestic mammals (in humans, amnion forms by cavitation deep to a persistent trophoblast). 3. Allantois — develops as an outgrowth of hindgut splanchnopleure (originates from inner cell mass). Allantois grows to fill the entire extra-embryonic coelom, with fluid-filled allantoic cavity in domestic mammals. The outer surface of allantois binds to the inner surface of chorion (and the outer surface of amnion). The allantois is highly vascular and provides the functional vessels of the placenta, via umbilical vessels. 4. Yolk sac — continuous with midgut splanchnopleure (develops early with hypoblast for- mation from inner cell mass). Supplied by vitelline vessels, it forms an early temporary placenta in the horse and dog. Yolk sac is most important in egg laying vertebrates. Note: The term conceptus refers to the embryo or fetus plus its fetal membranes. Implantation The blastocyst is initially free in the uterine lumen (nourished by uterine glands). Im- plantation of the blastocyct is a gradual process, beginning with apposition, leading to adhesion (or invasion in the case of the human & Guinea Pig). Approximate implantation times are: one week (human); two weeks (dog, cat, sheep), 3-5 weeks (cattle), 3-8 weeks horse; or delayed up to 4 mons (deer, bears). 15  Musculo-Skeletal System (Trunk, Limbs, and Head) General Statements: Mesoderm gives rise to skeletal muscle, skin dermis, endochondral bones and joints. Notochord induces paraxial mesoderm to form somites (somitomeres develop rostral to the somites somitomeres notochord in the head). in Each somite differentiates into three regions: pharyngeal arches — sclerotome (medial): forms most of the axial skeleton (vertebrae, ribs, and base of the skull). heart limb — dermatome (lateral): migrates to form eye bud dermis of the skin head — myotome (middle): migrates to form skeletal Somites & Somitomeres muscles. Individual adult muscles are produced by merger of adjacent myotomes. Note: Early in development, nerves make connections with adjacent myotomes and dermatomes, establishing a segmental innervation pattern. As myotome/dermatome cells migrate to assume adult positions, the segmental nerve supply must follow along to maintain its connection to the innervation target. (Recurrent laryngeal & phrenic nerves travel long distances because their targets migrated far away.) Skin. somite: Consists of dermis and epidermis: ectoderm dermatome Epidermis, including hair follicles & glands, myotome sclerotome is derived from ectoderm. Neural crest cells neural crest intermediate migrate into epidermis and become melanocytes. mesoderm neural tube (Other neural crest cells become tactile disc receptors.) somatic Dermis arises from dermatomes of somites. notochord mesoderm Adjacent dermatomes overlap; thus, each skin endoderm aorta region is innervated by 2 or 3 spinal nerves. coelom Muscle. splanchnic mesoderm All skeletal muscle is derived from paraxial Mesoderm Regions mesoderm which forms somites and, rostrally in the head, somitomeres. (The one exception is iris musculature, derived from optic cup ectoderm.) Cardiac and smooth muscles originate from splanchnic mesoderm. Myotome cells differentiate into myoblasts which fuse to form multinucleate myocytes (muscle fibers). The myocytes synthesize myosin & actin (the myofilaments align producing a striated muscle appearance). Developing muscles and tendons must be under tension (stretched by growing bone) in order to grow to proper lengths. Muscle development requires innervation. Muscles release trophic molecules that determine muscle cell type (I, IIa, IIb). Also, muscles release trophic molecules that affect nerve growth. Note: Each anatomical muscle is genetically allocated a specific number of myoblasts that is deter- mined by the time of birth. Thereafter, muscle cell growth is due solely to cellular hypertro- phy. Regeneration (hyperplasia) of adult muscle cells does not occur. 16 Bone. Most bones are formed endochondrally (ossification of cartilage precursor) Bones of the calvaria (top of the skull) & face are formed intramembranously (osteoblasts arise directly from ectomesenchyme cells rather than from chondroblasts) Embryologically, the skeleton originates from different sources: — paraxial mesoderm forms sclerotomes that give rise endochondrally to axial skeleton — somatic mesoderm forms endochondral appendicular bones per particular regions — ectomesenchyme from neural crest forms intramembranous bones of the calvaria and face. Endochondral bone formation: — local mesenchyme undergoes condensation and cells differentiate into chondroblasts — chondroblasts secrete matrix to produce a cartilage model of the future bone; the model is surrounded by perichondral fibrous tissue — the diaphysis of the cartilage model undergoes ossification first (primary ossification); epiphyseal ossification occurs later (secondary ossification) — physis ossification is postponed until bones stop growing in length. — overall bone shape is genetically determined; surface irregularities of bone are acquired due to localized tension (stress) produced by ligaments and tendons. Ligaments, Tendons & Fibrous Tissue originate from local mesenchyme or ectomesenchyme. Joints. — condensation of mesenchyme cavitation produces an interzone region within peri- perichondral synovial chondral tissue connecting adjacent carti- layer cavity lage models of bones interzone ligament — the interzone becomes fibrous cartilage connective tissue or fibrocartilage or a (bone) synovial membrane fibrous synovial cavity (according to the nature of capsule the future joint) Synovial Joint Development Synovial joint formation: — mesenchyme at the center of the interzone undergoes cavitation — tissue bordering the cavity become synovial membrane, uneven expansion of the cavity creates synovial folds — interzone mesenchyme also forms intra-articular ligaments where these are present — perichondral tissue surrounding the interzone becomes joint capsule and localized thickenings of the joint capsule forms ligaments Note: Nerve driven muscle activity is essential for proper synovial joint development after the joint cavity is formed. Joints must move during in utero and postnatal development to prevent ankylosis (fixed/frozen joint). Also, muscles must be stretched by growing bones in utero; other- wise, joints would be restricted by contracted muscles at birth. 17  epaxial Regional Specifics muscles dorsal Trunk Region: branch Skeletal Muscles. ventral — adjacent myotomes merge, forming broad muscles that are branch segmentally innervated (each myotome brings its own innervation hypaxial when it overlaps with adjacent myotomes). muscles — myotome accumulations segregate into a dorsal mass (epi- mere) innervated by dorsal branches of spinal nerves and a ventral mass (hypomere) innervated by ventral branches of spinal nerves. — epimere and hypomere masses subdivide, the epimere becomes epaxial muscles and the hypomere becomes hypaxial spinal nerve muscles. gut Axial Skeleton. — sclerotomes give rise to vertebrae and ribs. coelom — the sternum develops differently, from chondrification/ossification of Myotome local somatic mesenchyme of the ventral thorax. Segregation Formation of Vertebrae and Ribs: — somite sclerotomes migrate & become a continuous mass surrounding the notochord and neural tube. Thus the original so- mite segmentation is lost! — the continuous mass differentiates into diffuse & dense regions per original sclerotome — to produce a cartilage model of one vertebra, the diffuse region from one somite combines with the dense region of an adja- L-2 cent somite — intervertebral disc regions develop between newly formed vertebrae, sclerotome mesenchyme forms annulus fibrous and no- tochord forms nucleus pulposus (elsewhere notochord degenerates) — ribs develop as extensions of thoracic vertebrae processes Note: As a result of the above re-segmentation, vertebrae are shifted relative to other segmental structures (see next page). Consequently, muscles span adjacent vertebrae; L-3 spinal nerves traverse intervertebral foramina (located dorsal to intervertebral discs); and embryonic intersegmental arteries become spinal arteries that run along side vertebral bodies. The notochord, neural tube, and neural crest all play a role di- recting somite differentiation and vertebral segmentation (formation). Vertebral anomalies include: stenosis of the vertebral canal; mal-articulation; hemivertebra; and spinal bifida (absent vertebral arch). Note: The dens originates as the body of vertebra C1 (atlas), but it fuses with vertebra C2 (axis). Canine Dermatomes 18  Sclerotomes to Vertebrae neural tube dorsal root ectoderm neural tube segments spinal n. somite sclerotome notochord myotome caudal cranial dermatome continuous mass sclerotome myotome dense diffuse spinous process ossification transverse process vertebral rib canal tubercle rib head vertebral body notochord vertebra muscle intervertebral disc 19 Limbs: Skeletal Muscles. — hypomere myotomes along with their innervation migrate into the developing limb bud. — myotomes segregate initially into an extensor mass and a flexor mass — subsequently the two masses subdivide into the individual extensor muscles and flexor muscles. Appendicular Skeleton and Skin. — bone, cartilage, and connective tissue of the limb arise from the local somatic mesoderm of the limb bud. — local mesenchyme condenses and forms cartilage models of limb bones — dermis comes from dermatome migrations into the limb bud — vessels and nerves grow into the limb. Limb Morphogenesis: — limbs grow outward from body wall somatopleure as limb buds — a limb bud begins as a limb field (an area of somatopleure foot plate committed to forming a limb) — a limb bud is produced by localized proliferation & condensation of mesenchyme, surface covered by ectoderm — regions of the limb develop in proximal to distal order as the limb bud elongates (the shoulder/hip appears first, the manus/pes is the last to be added) — the distal end of the limb bud (footplate) is flattened like a paddle & ectoderm along its outer margin forms a thickened apical ridge cell death — the apical ridge is induced to form by underlying mesoderm and, in turn, it induces the mesoderm to continue growing into a limb) — mechanically, limb growth consists of: elongation of a dorsoventrally flattened limb bud digit ventroflexion of the distal half of the limb (ventral now faces medially) pronation of the distal half (previous medial surface now becomes caudal) — separate digits are produced by interdigital necrotic zones (species Manus/Pes with fewer digits undergo further degeneration and/or fusion of digits); Development Clinical considerations: Achondroplasia (dwarfism; Dachshund) — inherited, systemic, premature ossification of physes of extremities. Arthrogryposis [Gr. gryposis = crooked] can result from malformed joints, denervation, abnormal muscle tension, or impaired mobility in utero. Polydactyly (extra digits); syndactyly (fused digits); brachydactyly (stumpy digits) [Gr. dactylos = digit] Amelia (no limb); meromelia (absence of part of limb); micromelia (small limb) [Gr. melos = limb] Note: phocomelia (seal limb) = absence of proximal segment(s) of limb was a consequence of pregnant women taking thalidomide in the late 1950s. 20 Head Region: The head consists of a cranium (which contains the brain within a cranial cavity) and a face. The cranium is formed during growth of the head process; the face develops from outgrowths of the frontonasal process and first pharyngeal arch. Since the face and cranium have different embryonic origins, they can be independently influenced genetically (e.g., in the case of brachycephalic breeds) or by teratogens. Skeletal Muscles. Muscles of the head arise from myotomes derived from somitomeres (seven) or somites (four occipital somites: Somitomere myotomes migrate to the orbit (two giving rise eye muscles) or they migrate to pharyngeal arches (becoming muscles of mastication, facial expression muscles). Somite myotomes become tongue and neck muscles and they migrate to pharyngeal arches (IV-VI), becoming pharyngeal, laryngeal & esophageal muscles. Cranial nerves establish early connections with adjacent somitomeres & somites and accompany them to definitive muscle sites. Each pharyngeal arch is innervated by specific cranial nerves (I=trigeminal; II=facial; III=glossopharyngeal; IV-VI=vagus). Skull. Bones of the base of the cranium develop endochondrally; but the relatively flat bones that comprise the calvaria (roof of the cranium) and the face develop intramembranously. Endochondral bones are formed from the sclerotomes of somitomeres and the first four somites (occipital somites). Intramembranous bones arise from ectomesenchyme (derived from neural crest). Intramem branous bones articulate by means of fibrous joints called sutures. Widened suture areas, at the corners of growing bones, are called fontanels. Sutures and fontanels allow bony plates to overlap one another during parturition. The mandible has a complex origin involving both endochondral and intramembranous development. Auditory ossicles arise endochondrally from pharyngeal arches I (malleus & incus) and II (stapes). Note: Ectomesenchyme (mesenchyme derived from neural crest) gives rise to cartilage, bone, and connective tissue of the face and dorsal head (calvaria). Regions of the Skull calvaria of cranium (intramembranous ) face (intramembranous) base of cranium (endochondral ) 21 Pharyngeal Arch Summary: Ectomesenchyme fills pharyngeal arches and forms connective tissue, cartilage and bone. Somitomere/somite myotomes migrate into pharyngeal arches and give rise to the skeletal muscles that arise from that arch. Each arch is innervated by a particular cranial nerve. First arch. (innervated by cranial nerve V) — jaw bones (mandible & maxilla); also, ossicles of the middle ear (malleus & incus) — muscles of mastication, plus rostral digastricus, mylohyoid, & tensor tympani mm. Second arch: (innervated by cranial nerve VII) — hyoid bones & stapes (ossicle of the middle ear) — muscles of facial expression, including caudal digastricus & stapedius mm. Third arch: (innervated by cranial nerve IX) — hyoid bones — one pharyngeal muscle (stylopharyngeus mm.) Arches IV through VI: (innervated by cranial nerve X) — laryngeal cartilages — pharyngeal mm & cricothyroid m — innervated by cranial branch of X — intrinsic laryngeal mm — innervated by recurrent laryngeal n. of X 22  Formation of Body (Serous) Cavities Serous Body Cavities: Serous cavities are located within the trunk and lined by serous membrane (mesothelium). Adult, serous cavities are: — pericardial cavity, — two pleural cavities, and — peritoneal cavity, including the vaginal cavities (bilateral extensions of the peritoneal cavity). Serous cavity formation may be summarized as follows: all of the serous cavities develop from a common embryonic coelom; thus, the cavities are continuous until partitions develop to separate them; the individual serous cavities of the adult are formed by inward growth of tissue folds from the body wall (par- titions) and by outgrowth of coelomic cavity into the body wall (excavation). Coelom (Celom) Development: — primary mesenchyme forms mesoderm and cavita- tion within lateral mesoderm expands to establish a horseshoe shaped coelom bounded by somatopleure and splanchnopleure — as head and tail processes develop and lateral body folds merge medially (except at the umbilicus), embryonic and extra- embryonic coelomic compartments become differentiated; the former becomes the serous body cavities, the latter is chorionic — head process formation produces a foregut and brings the heart and pericardial coelom into the embryo, positioned ventral to the foregut. Right and left sides of the embryonic coelom are separated by gut and by dorsal and ventral mesenteries, but the latter fails to develop at the level of the midgut — thus, the embryonic coelom features an anterior-ventral pericardial compartment, a caudal peritoneal compartment, and bilateral pleural compartments connecting these Mesoderm = somite neural tube = intermediate notochord = lateral foregut Lateral Body Folds embryonic coelom mesentery somatopleure extra-embryonic splanchnopleure yolk coelom sac 23  — mesoderm lining the coelom forms mesothelium dorsal aorta neural tube limb vertebra esophagus lung bud aorta mediastinum pleural pleuro- lung coelom pericardial pleural cavity fold heart body wall pericardial coelom fibrous pericardium preicardial sac Early Pleural Cavity Formation Late Separation of Pericardial and Pleural Cavities: pericardial and pleural cavities are separated by fibrous pericardium in the adult. in the embryo, the pericardial coelomic cavity communicate with two dorsally positioned pleural cavities (canals) the cavities become partitioned initially by pleuropericardial folds and subsequently by somatic mesoderm. details of the separation include: — bilateral pleuropericardial folds (which accompany common cardinal veins) converge medially to unite with the mediastinum, partitioning the pericar- dial cavity from the pleural canals — subsequently, growing pleural cavities dissect ventrolaterally into the body wall, incorporating somatic mesoderm into fibrous pericardium. NOTE: Mediastinum is formed initially by dorsal and ventral mesenteries of the esophagus. Separation of Peritoneal and Pleural Cavities: adult peritoneal and pleural cavities are separated by the diaphragm the diaphragm is formed by a septum transversum, paired pleuroperitoneal folds, and somatic mesoderm NOTE: diaphragm muscle is derived from somites in the cervi- cal region (C5, 6, 7), where it initially develops Details of diaphragm formation include: — the septum transversum originates as mesoderm anterior the heart and becomes incorporated into the ventral body wall and mesentery caudal to the heart when the heart moves ventral to the foregut — the septum transversum grows dorsally and forms a transverse partition ventral to the level of the gut — dorsal to the gut, bilateral pleuroperitoneal folds grow medially and meet the septum transversum, completing the central tendon — subsequently, pleural cavities grow into body wall somatic mesoderm; myotomes migrate to this region which will contain diaphragm musculature Growth of Pleural Cavities: Initially pleural cavities are small canals into which lung buds project. As lungs grow, pleural cavities enlarge and carve into the body wall (into somatic mesoderm). Consequently, somatic mesoderm forms partitions (fibrous pericardium & diaphragm) that bound the pleural cavities. 24  Cardiovascular System Note: The cardiovascular system develops early (week-3), enabling the embryo to grow beyond the short distances over which diffusion is efficient for transferring O2, CO2, and cellular nutrients & wastes. Heart: Beginning as a simple tube, the heart undergoes differential growth into a four chambered struc- ture, while it is pumping blood throughout the embryo and into extra-embryonic membranes. Angiogenesis begins with blood island formation in splanchnic mesoderm of the yolk sac and allantois. Vessel formation occurs when island vesicles coalesce, sprout buds, and fuse to form vascular channels. Hematopoiesis (blood cell formation) occurs in the liver and spleen and later in the bone marrow. The transition from fetal to adult circulation involves new vessel formation, vessel merger, and degeneration of early vessels. Formation of a Tubular Heart: The first evidence of heart develop- amnionic cavity ment is bilateral vessel formation within the cardiogenic plate (splanchnic meso- embryo ectoderm derm situated anterior to the embryo). The cardiogenic plate moves ven- cardiogenic endoderm tral to the pharynx as the head process yolk sac plate mesoderm grows upward and outward. Bilateral endocardial tubes meet at the midline & fuse into a single endo- embryo cardial tube, the future heart. Splanchnic mesoderm surround- heart ing the tube forms cardiac muscle cells capable of pumping blood. yolk sac Primitive Heart Regions: Differential growth of the endocardial tube establishes five primitive heart regions: 1] Truncus arteriosus — the output region of the heart. It will develop into the ascending aorta and pulmonary trunk. truncus 2] Bulbus cordis — a bulb-shaped region des- arteriosus tined to become right ventricle. bulbus cordis 3] Ventricle — an enlargement destined to become the left ventricle. 4] Atrium — a region that will expand to be- ventricle come both right and left auricles. sinus 5] Sinus venosus — a paired region into L venosus L R which veins drain. The left sinus venosus atrium becomes the coronary sinus; the right is incor- R Midline Fusion porated into the wall of the right atrium. Tubular Heart 25 Forming a Four-Chambered Heart: The following are six snapshots of the development process: A] Endocardial tube lengthens and cranial loops on itself—this puts the bulbus truncus cordis (right ventricle) beside the ventricle arteriosus (left ventricle) and the atrium dorsal to the bulbus cordis atrium sinus ventricle. venosus B] Venous return is shifted to the bulbus right side: cordis common The larger right sinus venosus ventricle atrioventricular opening becomes the right atrium. (The em- ventricle atrium bryonic atrium becomes auricles.) sinus venosus The smaller left sinus venosus joins the future right atrium as the Sagittal Section coronary sinus. caudal Endocardial Tube The embryonic atrium expands and overlies the ventricle chamber. A common atrioventricular opening connects the two chambers. A constriction, the future coronary groove, separates atrium and the ventricle. C] Atrio-ventricular opening endocardial is partitioned: truncus cushion Growth of endocardial arteriosus atrium “cushions” partitions the com- atrium mon A-V opening into right and left openings. bulbus interventricular: Ventral growth of the cordis right foramen ventricle septum cushions contributes to a sep- ventricle left tum that closes the interven- ventricle tricular foramen (the original opening between the bulbus Ventricle cordis & ventricle). Development Incomplete closure of the inter- ventricular septum (ventricular septal defect) results in blood flow from the left to the right ventricle and an associated murmur. Large defects produce clinical signs of cardiac insufficiency. D] Right & left ventricles formed: secondary septum Ventral growth and interior excavation of sinuatrial the bulbus cordis and ventricle form right & opening secondary left ventricles, respectively. foramen The interventricular septum, atrioven- path of tricular valves, chordae tendineae, papillary blood flow muscles, and irregularities of the internal right primary septum ventricular wall are all sculptured by selective atrium (valve of f.ovale) excavation of ventricular wall tissue. foramen ovale E] Right and left atria divided by a septum: Septum formation is complicated by the need, until birth, for a patent (open) septum Blood Flow Through Foramen Ovale that allows blood to flow from the right atrium to the left. The septal opening is called the foramen ovale. 26  Formation of the interatrial septum and foramen ovale: Interatrial Septum 1 grows from the dorsal atrial wall toward the endocardial cushions. The pre-existing Foramen 1 is obliterated when Septum 1 meets the endocardial cushion. Foramen 2 develops by fenestration of the dorsocranial region of Septum 1 (before Foramen 1 is obliterated). Interatrial Septum 2 grows from the cranial wall of the right atrium toward the caudal wall. The septum remains incomplete and its free edge forms the boundary of an opening called the Foramen Ovale. NOTE: As long as blood pressure in the right atrium exceeds that of the left, blood enters the Foramen Ovale, flows between the two septae and exits into the left atrium. When, at birth, pressure is equal in the two atria, the left septum is forced against the Foramen Ovale, acting as a valve to preclude blood flow. An atrial septal defect is not a serious developmental anomaly as long as pressure is ap- proximately equal in the two atria, which is normally the case. F] Aorta and pulmonary trunk formed: aorta The truncus arteriosus (and adjacent bulbus cordis) is partitioned in a spiral pattern in order to form the aorta & caudal pulmonary trunk. vena cava pulmonary Ridges appear along the lumen wall, grow inward trunk left and merge to create the spiral septum. As a result, the right atrium aorta and pulmonary trunk spiral around one another. atrium Failure of the septum to spiral leaves the aorta connected to the right ventricle and the pulmonary trunk to the left ventricle—a fatal left flaw. right ventricle Growths from the spiral septum and endocardial cushions both ventricle contribute to proper closure of the interventricular septum. Aortic and pulmonary semilunar valves are formed like atrioventricular valves, by selective erosion of car- diac/vessel wall. Spiral Arrangement of the Improper valve sculpturing will produce valvular insufficiency Aorta & Pulmonary Trunk in the case of excessive erosion or vessel stenosis (narrow lumen) in cases of not enough erosion. Note: vessel wall excavation semilunar Neural crest cells mi- aorta or pulmonary trunk cusp grate to the region of the truncus arteriosus and direct its partition- ing by the spiral sep- tum. Ablation of the flow neural crest results in from anomalies of the great heart vessels. Development of semilunar valves by excavation Tetralogy of Fallot: This is a cardiac anomaly that occurs in number of species, including humans. It involves a combination of four defects all related to a defective spiral septum formation in the truncus arteriosus & bulbus cordis: ventricular septal defect; stenosis of the pulmonary trunk; enlarged aorta that overrides the right ventricle (dextroposition of the aorta); and hypertrophy of the right ventricle, secondary to communication with the high pressure left ventricle. 27  right intersegmental aa. dorsal aorta caudal cranial cardinal v. iliac vitelline a. cardinal v. branch umbilical a. common cardinal v. umbilical v. HEART aortic ventral vitelline v. arch aorta Early allantoic Arteries yolk sac vessels & Veins vessels Arteries: Paired ventral and dorsal aortae develop in the embryo. Bilaterally, ventral & dorsal aortae are connected by up to six aortic arches. Each aortic arch is situated within a pharyngeal arch. Caudal to the aortic arches, the paired dorsal aortae merge to form a single descending aorta, as found in the adult. The aorta gives off dorsal, lateral, and ventral branches, some of which persist as adult vessels. Paired ventral aortae receive blood from the truncus arteriosus and fuse to form the adult bra- chiocephalic trunk. Disposition of Aortic Arches: common aortic carotid a. The third, fourth, and sixth aortic arches become arch 3 adult vessels. The first two arches degenerate and the fifth arch internal is rudimentary or absent. carotid a. dorsal external aorta Each third aortic arch becomes an internal carotid carotid a. artery and proximally the third arch forms a common carotid artery. The dorsal aorta degenerates between the third degenerating and fourth aortic arches. Consequently, the third arch supplies dorsal aortic the head and the fourth arch supplies more caudal regions. The aorta arch 4 external carotid artery buds from the third arch. aortic ductus The left fourth aortic arch becomes the adult arch arteriosus arch 6 of the aorta. The right fourth aortic arch becomes the proxi- mal part of the right subclavian artery as the distal connection pulmonary a. right 7th between the arch and the dorsal aorta normally degenerates. intersegmental a. left 7th (Persistence of a connection between the fourth aortic arch and intersegmental a. degenerating the descending aorta results in compression of the esophagus, right dorsal aorta descending aorta accompanied difficult swallowing and an enlarged esophagus cranial to the compression.) Aortic Arches 3, 4, 6 The proximal part of each sixth aortic arch be- (Dorsal View) comes a pulmonary artery. The distal part of the arch degenerates on the right side but persists as ductus arteriosus on the left side. Note: The ductus arteriosus shunts blood from the pulmonary trunk to the aorta, allowing the right ventricle to be exercised in the face of limited blood return from the lungs. At birth, abrupt constriction of the ductus arteriosus shifts pulmonary trunk output into the lungs. Eventually, a ligamentum arte- riosum replaces the constricted ductus arteriosus. (A persistent ductus arteriosus results in a continuous murmur during both systole and diastole.) 28 Subclavian & Vertebral arteries: Each dorsal aorta gives off intersegmental arteries that pass dorsally between somites. Bilaterally, the seventh cervi- cal intersegmental artery becomes the distal portion of the subclavian artery. Intersegmental arteries cranial to the seventh cervical form the vertebral artery (by anastomosing with one another and losing connections to the aorta via degeneration). Intersegmental arteries caudal to the seventh cervical become intercostal and lumbar arteries. When the heart shifts caudally from the neck to the thoracic cavity, positions of aortic arch arteries are changed. In particular the subclavian arteries becomes transposed from a position caudal to the heart to a cranial position. Branches of Dorsal Aortae: Right and left vitelline arteries arise from right and left dorsal aortae to supply the yolk sac. The right vitelline artery becomes the adult cranial mesenteric artery. The left vitelline artery normally degenerates. (Incomplete degeneration of the left vitelline artery can result in a fibrous band that may cause colic by entrapping a segment of intestine.) Each dorsal aorta terminates in an umbilical artery that supplies blood to the allantois. In the adult, umbilical arteries persist to the urinary bladder and degenerate distal to the bladder. External and internal iliac arteries develop as outgrowths of the umbilical artery. Veins: Bilaterally, the embryonic sinus venosus receives: — vitelline veins, which drain the yolk sac — umbilical veins which drain the allantois, and — cardinal veins which drain the embryo. The transition from embryonic to adult venous patterns involves the formation of new veins, anastomoses between veins, and the selective degeneration of embryonic segments. Note: Recall that venous return is shifted Cranial Vena Cava to the right side and the right sinus Development (Dorsal View) venosus is incorporated into the right atrium. The left sinus venosus is re- external jugular v. duced and becomes coronary sinus. L. sub- R. sub- calavian calavian Cranial Vena Cava Formation: v. v. Each cranial cardinal vein becomes the adult internal jugu- brachio- lar vein. The much larger external jugular and subclavian veins cephalic vv. arise by budding from the cranial cardinal vein. An anastomotic vein develops and runs from left to right degenerated cranial cardinal veins, shifting venous return to the right side and left cranial becoming left brachiocephalic vein. (Failure of the anastomotic cardial v. vein to develop results in a double cranial vena cava, the typical anastomotic cranial condition in rats and mice.) branch vena cava The caudal segment of right cranial cardinal vein along with the right common cardinal vein becomes the cranial vena cava. Caudal Vena Cava and Azygos Vein: coronary caudal Each caudal cardinal vein gives rise to supra-cardinal and sinus right atrium vena cava sub-cardinal veins with extensive anastomoses among all of the veins. These venous networks, located in intermediate meso- derm, supply embryonic kidneys and gonads. Selective segments of particularly the right subcardinal venous network, including an anastomosis with the proximal end of the right vitelline vein form the caudal vena cava. The azygos vein develops from the supracardinal vein as well as the caudal and common cardinal veins of the right side (dog, cat, horse) or the left side (pig) or both sides (ruminants). The azygos vein will drain into the cranial vena cava (or right atrium) on the right side and into the coronary sinus on the left side. 29 Portal Vein and Ductus Venosus: Proximally, vitelline veins form liver sinu- heart atrium common soids as the developing liver surrounds the veins. cardianl v. sinus Vitelline veins gives rise to the portal vein, formed venosus by anastomoses that develop between right and left vitelline veins and enlargement/atrophy of selective caudal anastomoses. cranial cardinal v. cardinal v. Umbilical veins, also engulfed by the de- veloping liver, contribute to the formation of liver liver degenerating sinusoids. Within the embryo, the right umbilical sinusoids segment vein atrophies and the left conveys placental blood right to the liver. Within the liver, a shunt, the ductus umbilical LIVER venosus, develops between the left umbilical vein v. and the right hepatic vein which drains into the left vitelline v. caudal vena cava. umbilical v. Postnatally, the left umbilical vein becomes the FOREGUT round ligament of the liver located in the free edge of the Vitelline & Umbilical Veins falciform ligament. (Ventral View) Because a fetus is not eating & because the placenta is able to detoxify blood & because it is mechanically desirable for venous return to bypass fetal liver sinusoids, the ductus venosus develops in the embryo as a shunt that di- verts blood away from sinusoids and toward systemic veins. Postnatally, however, a persistent portosystemic shunt allows toxic diges- tive products to bypass the liver. These toxic agents typically affect the brain resulting in neurologic disorders at some time during life. A portosystemic shunt can be the result of a persistent ductus venosus or a developmental error that results in anastomosis between the portal vein and the caudal vena cava or the azygos vein. Since adult veins are established by patch- ing together parts of embryonic veins, it is not surprising that mis-connections arise from time to time. Pulmonary Veins: These develop as outgrowth of the left atrium. The initial growth divides into left and right branches, each of which subdivides into branches that drains lobes of the lung. Pulmonary branches become incorporated into the wall of the expanding left atrium. The number of veins entering the adult atrium is variable due to vein fusion. Lymphatics: Lymph vessel formation is similar to blood angiogenesis. Lymphatics begin as lymph sacs in three regions: jugular (near brachiocephalic veins); cranial abdominal (future cysterna chyla); and iliac region. Lym- phatic vessels (ducts) form as outgrowths of the sacs. mesenchyme Lymph nodes are produced by localized mesodermal invaginations that partition the vessel lumen into sinusoids. The mesoderm develops a reticular framework within which lympho- sinusoid lymph duct lumen cytes accumulate. mesodermal The spleen and hemal nodes (in ruminants) develop similar to the invagination way lymph nodes develop. Lymph Node Formation 30  Prior to birth, fetal circulation is designed for the in utero aqueous environment, where the placenta oxygenates fetal blood. Suddenly, at birth... The environment is changed: Three In-Utero Adjustments Stretching and constriction of um- bilical arteries shifts fetal blood flow ductus from the placenta to the fetus. arteriosus aortic arch Reduced venous return through the pulmonary trunk (left) umbilical vein and ductus venosus L atrium allows the latter to gradually close (over foramen ovale R a period of days). atrium caudal vena cava Bradykinin being released by ex- panding lungs, a loss of prostaglandins generated by the placenta, and increased ductus venosus oxygen concentration in blood, all aorta combine to trigger rapid constriction of the ductus arteriosus which, over liver two months, is gradually converted to a fibrous structure, the ligamentum umbilical v. arteriosum. portal v. The increased blood flow to the lungs and then to the left atrium equal- izes pressure in the two atria, resulting umbilical aa. in closure of the foramen ovale that eventually grows permanent. 31  Digestive System NOTE: The digestive system consists of the: mouth (oral cavity); pharynx; esophagus; stomach; small intestine; colon and cecum; rectum; anal canal; and the liver, pancreas, and salivary glands. Development of head and tail processes, and the merger ventrally of lateral body folds, trans- forms splanchnopleure into: foregut, hindgut, & midgut (the latter is continuous with the yolk sac). Endoderm becomes epithelium lining of the digestive tract; splanchnic mesoderm forms con- nective tissue and smooth muscle components (except that ectoderm forms epithelium lining the proctodeum (caudal end of anal canal) and stomadeum (mouth & some salivary glands — parotid, zygomatic, labial & buccal). Foregut becomes pharynx, esophagus, stomach, cranial duodenum, and liver foregut midgut hindgut and pancreas. Midgut becomes the remaining small intestines, cecum, ascending colon, and pharynx part of the transverse colon. Hindgut becomes transverse and descending colon and a cloaca which forms the rectum and most of the anal canal. cloaca In the adult abdomen, derivatives of the foregut, midgut, and hindgut are those structures supplied by the celiac, cranial mesenteric, and caudal mesenteric yolk allantois arteries, respectively. sac Pharynx... The adult pharynx is a common respiratory-digestive stomach pancreas chamber. Initially, the pharynx is closed cranially by an oropha- trachea liver gall bladder ryngeal membrane that must degenerate to allow: pharyngeal Alimentary — the pharynx to com- municate with oral and nasal pouches Canal midgut cavity outgrowths; diverticulum — migration of tongue cecum muscle from the pharynx into the oral cavity. Pharyngeal pouches appear during development and give rise to allantois several adult structures, two of which retain continuity with the pharyn- geal cavity: auditory tube and fossa of the palatine tonsil. A midline evagination of the floor of the pharynx (laryngotracheal cloaca groove) gives rise to the larynx, trachea and lungs. Esophagus... The esophagus develops from foregut, caudal to the pharynx. Its principal morphogenic devel- opment is elongation. Skeletal muscle associated with both the esophagus & pharynx is derived from somites that migrate to the pharyngeal arches IV & VI (innervation is from vagus nerve). NOTE: Esophagus may be coated by skeletal muscle: throughout its length (dog, ruminants), to the level of the diaphragm (pig), to the mid-thorax (cat, horse, human), or not at all (avian). 32  SIMPLE STOMACH DEVELOPMENT LEFT DORSAL VIEW RIGHT esophagus esophagus lesser ✪ curvature dorsal border fundus dorsal border stomach duodenum