CPM 282 General and Systemic Embryology PDF

General and systemic Embryology Department of Clinical Pharmacy and Pharmacy Management, Faculty of Pharmaceutical science University of Nigeria Nsukka Pharm. Dr (Mrs.) CHIGOZIE GLORIA ANENE- OKEKE Neuroanatomy for Pharmacy Students CPM 282...

General and systemic Embryology Department of Clinical Pharmacy and Pharmacy Management, Faculty of Pharmaceutical science University of Nigeria Nsukka Pharm. Dr (Mrs.) CHIGOZIE GLORIA ANENE- OKEKE Neuroanatomy for Pharmacy Students CPM 282 January 2025 OUTLINE 1. Introduction 2. Cell division (mitosis, meiosis I & II) 3.Gametogenesis 4. Fertilization 5. Cleavage 6. Placenta 7. Gastrulation 8. Neurulation Introduction Embryology is a branch of biology that studies the pre-natal development of an embryo, starting from the development of sex cells/gametes, through the fertilization of the ovum (female sex cell/gamete) by a viable spermatozoon (male sex cell/gamete), formation of pluripotent (many cells capable of further differentiations) stem cells, to the differentiation into foetal tissues and organs. Embryology involves two major developmental studies. These include Embryonic Development: This involve all stages from fertilization, through cleavage of the zygote, formation of germ layers to differentiation of the germ layers into the organs of the body (organogenesis/ embryogenesis). During these stages, the developing life is referred to as an embryo.  Gestation period Germinal period- from 1st to 2nd week Embryonic period–from 3rd to 8th week Foetal period –from 9th week (3rd month) to termination of pregnancy Time period: day 0 to birth Embryonic period The embryonic period is considered to be the period from fertilization to the end of the eighth week. The period from fertilization to implantation of the blastocyst into the uterus (2 weeks) is sometimes called the period of the egg. During the period of the egg the early zygote rapidly proliferates to produce a ball of cells that makes its way along the uterine tube towards the uterus. The complexity of the blastocyst increases as it progresses towards the site of implantation. During the embryonic period the major structures of the embryo are formed, and by 8 weeks most organs and systems are established and functioning to some extent, but many are at an immature stage of development. At the end of the eighth week the external features of the embryo are recognizable; the eyes, ears and mouth are visible, the fingers and toes are formed, and limbs have elbow and knee joints. Foetal period From the ninth week to birth the foetus matures during the foetal period. The foetus grows rapidly in size, mass and complexity, and its proportions change (for example, head to trunk, and limbs). The foetus’ weight increases considerably in the latter stages of the foetal period. Organs and systems continue in their functional development, and some systems change considerably at birth (for example, the respiratory and circulatory systems). Birth in humans normally occurs between 37 and 42 weeks after fertilization. Cell division Cell division normally occurs in eukaryotic organisms through the process of mitosis, in which the maternal cell divides to form two genetically identical daughter cells. This allows growth, repair, replacement of lost cells and so on. A key process during mitosis is the duplication of DNA to give two identical sets of chromosomes, which are then pulled apart and new cells are formed around each set. The new cells may be considered to be clones of the maternal cell. The cell cycle includes phases G1 (gap 1), S (synthesis) and G2 (gap 2). DNA is duplicated (synthesised) during S phase. Mitosis A cell dividing by mitosis passes through phases. Interphase: including preparing for and doubling its DNA to form pairs of chromosomes) Prophase: DNA condenses to become chromosomes which are visible under a microscope. Centrioles move to opposite ends of the cell and extend microtubules out (this is the mitotic spindle). The centromeres at the center of the chromosomes also begin to extend fibres outwards Mitosis  Prometaphase: the nuclear membrane disappears, microtubules attach centrioles to centromeres and start pulling the chromosomes. Metaphase: chromosomes become aligned in the middle of the cell. Anaphase: chromosome pairs split (centromeres are cut), and one of each pair (sister chromatids) move to either end of the cell. Telophase: sister chromatids reach opposite ends of the cell and become less condensed and no longer visible; new membranes form around the new nuclei for the daughter cells. Cytokinesis: an actin ring around the center of the cell shrinks and splits the cell in two. Cell division by mitosis gives no opportunity for change or diversity, which is ideal for processes like growth and repair. In humans, sexual reproduction allows random mingling of maternal and paternal DNA to produce a new, unique individual. This is able to occur because of a different type of cell division called meiosis. Meiosis During meiosis a single cell divides twice to form four new cells. These daughter cells have half the normal number of chromosomes (they are haploid cells). Meiosis is the method of producing spermatozoa and oocytes. When an egg is fertilized by a sperm the chromosomes will combine to form a cell with the normal number of chromosomes. Human chromosomes There are 23 pairs of human chromosomes in a normal, diploid cell. Each chromosome is a length of DNA wrapped into an organized structure Twenty- two of the pairs of chromosomes are known as autosomes. The remaining pair are known as the sex chromosomes, which hold genes linked to the individual’s sex. When condensed the pairs of autosomes look like X’s and the sex chromosomes look like X’s or Y’s. The female sex chromosome pair appears as XX, the male as XY. Meiosis I A cell dividing by meiosis divides twice (meiosis I and meiosis II). During meiosis I, a cell passes through phases very similar to those of mitosis, but with some significant differences. It begins with 23 pairs of chromosomes (46 chromosomes in total). Interphase: the cell goes about its normal, daily business (diploid). Prophase I: homologous chromosomes exchange DNA (homologous recombination); chromosomes condense and become visible; centrioles move to opposite ends of the cell and extend microtubules out (mitotic spindle); centromeres extend fibres out from chromosomes (diploid). Prometaphase I: the nuclear membrane disappears, microtubules attach centrioles to centromeres and start pulling the chromosomes (diploid). Metaphase I: chromosomes are aligned in the middle of the cell (diploid). Anaphase I: homologous chromosome pairs split, one of each pair (each pair has two chromatids) moving to either end of the cell (diploid). Telophase I: homologous chromosomes reach each end of the cell; new membranes form around the new nuclei for the daughter cells (diploid). Cytokinesis: an actin ring around the centre of the cell shrinks and splits the cell in two (haploid). After meiosis I each cell has 23 chromosomes, and each chromosome has two chromatids. Meiosis II Without replicating its DNA the cell moves from meiosis I to meiosis II. Meiosis II is very similar to mitosis. Prophase II: chromatids condense and become visible; centrioles move to opposite ends of the cell and extend microtubules out (mitotic spindle); centromeres extend fibres out from chromosomes (haploid). Prometaphase II: the nuclear membrane disappears, microtubules attach centrioles to centromeres and start pulling the chromosomes (haploid). Metaphase II: chromosomes are aligned in the middle of the cell (haploid). Anaphase II: chromosome pairs split (centromeres cut), one of each pair (sister chromatids) moving to either end of the cell (haploid). Telophase II: sister chromatids reach opposite ends of the cell; new membranes form around the new nuclei for the daughter cells (haploid). Cytokinesis: an actin ring around the center of the cell shrinks and splits the cell in two (haploid). The end result is, 4 cells with 23 unpaired chromosomes each Gametogenesis Gametogenesis is typically divided into four phases: (1) the extraembryonic origin of the germ cells and their migration into the gonads, (2) an increase in the number of germ cells by mitosis, (3) a reduction in chromosomal number by meiosis, (4) structural and functional maturation of the eggs and spermatozoa. The first phase of gametogenesis is identical in males and females, whereas distinct differences exist between the male and female patterns in the last three phases. Phase 1: Origin and Migration of Germ Cells Primordial germ cells, the earliest recognizable precursors of gametes, arise outside the gonads and migrate into the gonads during early embryonic development. Human primordial germ cells first become readily recognizable at 24 days after fertilization in the endodermal layer of the yolk sac by their large size and high content of the enzyme alkaline phosphatase. Germ cells exit from the yolk sac into the hindgut epithelium and then migrate through the dorsal mesentery until they reach the primordia of the gonads Phase 2: Increase in the Number of Germ Cells by Mitosis After they arrive in the gonads, the primordial germ cells begin a phase of rapid mitotic proliferation. In a mitotic division, each germ cell produces two diploid progeny that are genetically equal. Through several series of mitotic divisions, the number of primordial germ cells increases exponentially from hundreds to millions. The pattern of mitotic proliferation differs markedly between male and female germ cells. Mitotically active germ cells in the female are called Oogonia through a period of intense mitotic activity in the embryonic ovary from the second through the fifth month of pregnancy in the human. During this period, the population of germ cells increases from only a few thousand to nearly 7 million. This number represents the maximum number of germ cells that is found in the ovaries. Shortly thereafter, numerous oogonia undergo a natural degeneration called atresia. Atresia of germ cells is a continuing feature of the histological landscape of the human ovary until menopause.  Spermatogonia, which are the male counterparts of oogonia, follow a pattern of mitotic proliferation that differs greatly from that in the female. Mitosis also begins early in the embryonic testes, but in contrast to female germ cells, male germ cells maintain the ability to divide throughout postnatal life. The seminiferous tubules of the testes are lined with a germinative population of spermatogonia. Beginning at puberty, subpopulations of spermatogonia undergo periodic waves of mitosis. The progeny of these divisions enter meiosis as synchronous groups. This pattern of spermatogonial mitosis continues throughout life.  Phase 3: Reduction in Chromosomal Number by Meiosis Of primary importance are (1) reduction of the number of chromosomes from the diploid (2n) to the haploid (1n) number so that the species number of chromosomes can be maintained from generation to generation (2) independent reassortment of maternal and paternal chromosomes for better mixing of genetic characteristics (3) further redistribution of maternal and paternal genetic information through the process of crossing-over during the first meiotic division. The first meiotic division, is often called the reductional division. Meiosis in Females The period of meiosis involves other cellular activities in addition to the redistribution of chromosomal material. As the oogonia enter the first meiotic division late in the fetal period, they are called primary oocytes.  Meiosis in Males Meiosis in the male does not begin until after puberty. In contrast to the primary oocytes in the female, not all spermatogonia enter meiosis at the same time. Large numbers of spermatogonia remain in the mitotic cycle throughout much of the reproductive lifetime of males. When the progeny of a spermatogonium have entered the meiotic cycle as primary spermatocytes Fertilization Fertilization is the process by which male and female gametes fuse together and this occur in the ampullary region of the uterine tube, which is the widest part of the tube and it is close to the ovary. Spermatozoa may remains viable in the female reproductive tract for several days. Only 1% of sperm deposited in the vagina enters the cervix, where they may survive for many hours. Movement of sperm from the cervix to the uterine tube occurs by muscular contractions of the uterus and uterine tube and very little by their own propulsion. The trip from the cervix to oviduct can occur as rapidly as 30 minutes or as slow as 6 days. After reaching the isthmus sperm becomes less motile and cease their migration. At ovulation, sperm again become motile, perhaps because of chemo attractants produced by cumulus cells surrounding the egg and swim to the ampulla, where fertilization usually occurs.  Spermatozoa are not able to fertilize the oocyte immediately upon arrival in the female genital tract but must undergo Capacitation Acrosome reaction to acquire this capability Capacitation Is a period of conditioning in the female reproductive tract (Humans) that lasts about 7 hours. Thus speeding to the ampulla is not an advantage because capacitation has not yet occurred and such sperm are not capable of fertilizing the egg. This conditioning during capacitation occurs in the uterine tube and involves epithelial interactions between the sperm and the mucosal surface of the tube. During this time a glycoprotein coat and seminal plasma proteins are removed from the plasma membrane that overlies the acrosomal region of the spermatozoa. Only capacitated sperm can pass through the corona cells and undergo the acrosome reaction. Acrosome reaction occurs after binding to the zona pellucida. Which is induced by zona proteins. This reaction culminates in the release of enzymes needed to Phases of fertilization Includes the following Phase 1;penetration of the corona radiata Phase 2 ; penetration of the zona pellucida Phase 3; fusion of the oocyte and sperm cell membrane Phase 1 Of the 200 to 300 million spermatozoa normally deposited in the female genital tract, only 300 to 500 reach the site of fertilization. Only one of these fertilize the egg. It is thought that the others aids the fertilizing sperm in penetrating the barriers protecting the female gamete. Capacitated sperm pass freely through corona cells. Phase 2 The zona is a glycoprotein shell surrounding the egg that facilitate and maintains sperm binding an induces the acrosome reaction. Both binding and the acrosome reaction are mediated by the ligands ZP3, a zona protein. Release of acrosomal enzymes (acrosin) allows sperm to penetrate the zona , thereby coming in contact with the plasma membrane of the oocyte. Permeability of the zona pellucida changes when the head of the sperm comes in contact with the oocyte surface. This contact results in release of lysosomal enzymes from cortical granules lining the plasma membrane of the oocytes.  In turn, these enzymes alter properties of the zona pellucida (zona reaction) to prevent sperm penetration and inactivate species-specific receptors sites for spermatozoa on the zona surface. Other spermatozoa have been found embedded in the zona pellucida, but only one seems to be able to penetrate the oocyte. Phase 3 The initial adhesion of sperm to the oocyte is mediated in part by the interaction of integrins on the oocyte and their ligands, disintegrins, on sperms. After adhesion, the plasma membranes of the sperm and the egg fuse. Because the plasma membrane covering the acrosomal head cap disappears during the acrosome reaction, actual fusion is accomplished between the oocyte membrane and the membrane that covers the posterior region of the sperm head. In the man, both the head and the tail of the spermatozoon enter the cytoplasm of the oocyte, but the plasma membrane is left behind on the oocyte surface. As soon as the spermatozoon has entered the oocyte, the egg responds in three ways Cortical and zona reaction Resumption of the second meiotic division Metabolic activation of the egg  Immediately after DNA synthesis, chromosomes organize on the spindle in preparation for a normal mitotic division. The 23 maternal and 23 paternal (double) chromosomes split longitudinally at the centromere, and sister chromatids move to opposite poles, providing each cells of the zygote with the normal diploid number of chromosomes and DNA. The sister chromatids move to opposite poles, a deep furrow appears on the surface of the cell, gradually dividing the cytoplasm into two parts. The results of fertilization are as follows restoration of the diploid number of chromosomes- half from the father and half from the mother. Hence, the zygote contains a new combination of chromosomes different from both parents. Determination of the sex of the new individual- An X carrying sperm products a female (XX) embryo, and a Y-carrying sperm produces a male (XY) embryo. The chromosomal sex of the embryo is determined at fertilization Initiation of cleavage- without fertilization the oocyte usually degenerates 24 hours after ovulation.  Cleavage Around 24 hours after fertilization the zygote begins to increase its number of cells by rapid mitosis, but without increasing its size. The cells become smaller with each cell division. The number of cells doubles with each division. This is cleavage. The cells of the zygote are called blastomeres. ; The two-cell stage is reached approximately 30 hours after fertilization, the 4-cell stage is reached approximately 40 hours. The 12- to 16 cell stage is reached at approximately after 3 days; and the late morula stage is reached at approximately 4 days. During this period, blastomeres are surrounded by the zona pellucida, which disappears at the end of the 4th day  Morula Cells become compacted and tightly squashed together. From around the 12-cell stage the ball of cells becomes called the morula (mulberry) , which it now resembles. The cells of the morula will not only give rise to the cells of the embryo, but also to many of its supporting structures, such as part of the placenta. By this stage the cells are communicating with each other and becoming organised and ready for the next stage. The blastomeres in the middle of the morula become the inner cell mass or embryoblast. These cells will directly form the embryo. The blastomeres on the outside of the morula become the outer cell mass or trophoblast. These cells will form some of the supporting structures for the embryo. Blastocyst The morula passes into the uterus around 4 days after fertilization. Trophoblast cells pull luminal fluid from the uterine cavity into the center of the morula. The fluid-filled space that forms is called the blastocoel (or blastocyst cavity). The cells of the inner cell mass are pushed to one end of the cavity and become called the embryonic pole. The morula is now called a blastocyst. Implantation Around 5 days after fertilization the blastocyst loses the zona pellucida. By doing this it becomes able to grow in size and interact with the uterine wall. The blastocyst attaches to the endometrial epithelium lining the uterus, triggering changes to the trophoblast and to the endometrium in preparation for the implantation of the blastocyst into the uterine wall. Implantation occurs at day 6-7 , Implantation occurs to enable the developing embryo to take oxygen and nutrients from the mother, thus enabling its growth.  Blastocyst Day 6-7 event during the first week: fertilization to implantation Day 6-7 event during the first week: fertilization to implantation  Implantation mechanism The location for implantation is commonly superiorly on the anterior or posterior walls of the uterus At implantation the blastocyst comprises a fluid-filled core, an outer cell mass (trophoblast) and an inner cell mass (embryoblast) at the embryonic pole. The process of implantation can be broken down into four stages. The first is hatching, as the developing blastocyst has to ‘hatch’ out of its surrounding zona pellucida. Apposition follows, as the trophoblast cells come into contact with the decidua of the endometrium. If the embryonic pole is not closest to the area of contact the inner cell mass rotates to become aligned with the decidua. Then adhesion occurs and molecular communication between blastocyst and endometrial cells is vastly increased. Finally, invasion of the endometrium by the trophoblast begins. Twins Twinning can occur in different ways. Two separate blastocysts may form from fertilisation by different sperm of two different ova released from an ovary simultaneously. These twins would not be identical twins, and they would have separate placentas (dichorionic), separate amniotic sacs (diamniotic) and may even be of different sexes. These would be dizygotic twins (or fraternal or non-identical twins). A zygote may split during cleavage, or later, when the inner cell mass has formed, or later still, when the embryo has become more complicated and formed a bilaminar embryonic disc. If the zygote splits during cleavage each blastocyst will implant separately. If the zygote splits at a later stage the two embryos may share the same chorion, amnion or placenta.  If a single zygote splits identical twins will grow. These twins would come from the same ovum and spermatozoon, so would be genetically identical. These would be monozygotic twins (or identical twins). This is rarer. It is common for monozygotic twins to share a placenta (monochorionic), but have separate amniotic sacs (diamniotic). This situation arises from cleavage of the blastocyst 4–8 days after fertilization. A small number of monozygotic twins share their amnion (monoamniotic), and this occurs if the division of the zygote occurs later than 9 days after fertilization. The more tissues shared between twins the greater the risk to the embryos. Hence, dizygotic twins have the lowest mortality risk. Conjoined twins are at significant risk. This situation arises when the zygote splits incompletely later than 12 days after fertilization. Bilaminar germ disc By day 8 implantation has begun and the blastocyst develops again into a more complex structure. The inner cell mass differentiates into an epiblast layer and a hypoblast layer. The hypoblast layer is located nearer to the blastocyst cavity. These two layers are now called the bilaminar disc. Simultaneously another cavity forms within the epiblast, called the amniotic cavity. The cells of the hypoblast will develop into the extraembryonic membranes (amnion, yolk sac, chorion and allantois) and the epiblast will develop to form the embryo Placenta Time period: day 7 to week 12 As the human embryo grows its need for nutrition increases, requiring a connection to the mother for nutrient, gas and waste exchange. The placenta develops to meet these needs. Trophoblast The trophoblast develops from the outer layer of the blastocyst before implantation into the endometrium. Trophoblast cells produce human chorionic gonadotrophin (hCG). Around 6–7 days after fertilization the trophoblast begins to invade the endometrium, triggering the decidual reaction and the process that will form the placenta from both embryonic and maternal tissues. The trophoblast layer has important roles in implantation and placental development, and protects the embryo from maternal immunological attack. With implantation the trophoblast divides into two layers ;the Gastrulation  Third week of gestation is the formation of the trilaminar disc. The process by which this takes place is called gastrulation. gastrulation produces the three germ layers (ectoderm, mesoderm and endoderm) from which embryonic structures will develop. Gastrulation is initiated at about day 14 or 15 with the formation of the primitive streak. The primitive streak runs as a depression on the epiblastic surface of the bilaminar disc and is restricted to the caudal half of the embryo. Towards the cephalic end there is a round mound of cells called the primitive node, surrounding the primitive pit. Epiblast cells migrate towards the streak and when they reach it they invaginate or slip under the epiblast layer to form new layers. The first cells to invaginate replace the hypoblast layer and produce the endodermal layer.  Some epiblast cells form the mesodermal layer between the epiblast layer and the endodermal layer. Cells migrating through the lateral part of the primitive node and cranial part of the streak become paraxial mesoderm, cells migrating through the mid-streak level become intermediate mesoderm and cells that migrate through the caudal part of the streak are destined to be lateral plate mesoderm Cells that migrate through the most caudal tip of the streak contribute to the extra-embryonic mesoderm, along with the cells of the hypoblast. The epiblast layer now becomes the ectodermal layer. After cells have migrated through the streak and begun their path to specialization, they continue to travel to different areas of the embryo. The first cells that travel towards the cephalic end form the prechordal plate, inferior to the buccopharyngeal (or oropharyngeal) Ectoderm – epidermis, peripheral nervous system, central nervous system, retina, cornea, lens, sclera. Mesoderm - The mesoderm is a major contributor to the embryo and its cells are used to build the bones, cartilage and connective tissues of the skeleton, striated skeletal muscle, smooth muscle, most of the cardiovascular system and lymphatic system, the reproductive system,  kidneys, the suprarenal cortex, ureters, the linings of body cavities such as the peritoneum, the dermis of the skin and the spleen. Cells of the cardiovascular and immune systems formed in the bone marrow are also derived from mesoderm. Endoderm- Epithelia derived from endoderm line internal passages exposed to external substances, including the gastrointestinal tract, the lungs and respiratory tracts. Glands that open into the gastrointestinal tract and the glandular cells of organs associated with the gastrointestinal tract, such as the pancreas and liver, are also derived from the endoderm. The epithelia of the urethra and bladder, tonsils, the thymus, the thyroid gland and the parathyroid gland. Neurulation This occur at day 18 – 28.The formation of the neural tube from a flat sheet of ectoderm is called neurulation. The initially simple tube will develop and form the brain, spinal cord and retina, and is the source of neural crest cells and their derivatives Notochord As cells of the epiblast pass through the primitive streak during gastrulation, some of those cells are destined to form a distinct collection of cells in the midline of the developing embryo. The primitive node extends as a tube of mesenchymal cells running in the midline of the embryo between the ectoderm and endoderm. This is the notochordal process. It grows and extends in a cranial direction developing a lumen. Around day 20 the notochordal process fuses with the endoderm beneath it, forming the notochordal plate. A couple of days later the cells of the notochordal plate lift from the endoderm and form a solid rod, again running almost the full length of the midline of the embryo. This is the notochord. Neural plate The notochord is a signalling center that signals to the cells of the overlying ectoderm. As the notochord forms the ectoderm in the midline of the embryo thickens, becoming the neural plate from day 18. Now the ectoderm is becoming neuroectoderm. This begins at the cranial end of the embryo and extends towards the caudal end. The neural plate is broader cranially, and this will form the brain. The remainder of the neural plate elongates and develops into the spinal cord. Neural tube The neural plate dips inwards in the midline, beginning to fold and form a neural groove. The sides of the groove are the neural folds, and the parts of neuroectoderm brought towards one another to meet are the neural crests. The neural crests look like the crests of two waves crashing into each other to complete the tube. The two sides of the neural plate are brought together, meet and fuse, forming a self-contained tube of neuroectoderm running the length of the embryo, open at either end. This is the neural tube. The neural tube separates from the ectoderm, which reforms over the neural tube, forming the external surface of the embryo. Development of the neural tube from the neural plate extends cranially and caudally, leaving either end open at the cranial and caudal neuropores. The cranial neuropore closes on day 24 and the caudal neuropore closes on day 26. Neurulation is now complete. Neural crest cells As the neural tube forms from the neural plate a new cell type appears in the neural crest. These are neural crest cells and as the neural tube forms these cells leave the neural tube and migrate away to other parts of the embryo. They become parts of a wide range of organs and structures, and differentiate to form a variety of different cell types. such as, they will form much of the peripheral nervous system, skeletal parts of the face and pigment cells in the skin (melanocytes). Migration and differentiation of these cells is well organized and an important part of the normal development of much of the embryo. Development of the central nervous system (somites) From neurulation the central nervous system continues to develop as the Neural cranial end of the neural tube dilates andfold folds to form spaces that will become the brain. The remainder of the neural tube, caudal to the first 4 somites, will become the spinal cord. Cells of the walls of the tube differentiate and proliferate to become neurons, glial cells and macroglial cells, and the walls thicken.  Clinical relevance The most common congenital abnormalities of. If the spinal cord or nerve roots also protrude this neurulation are neural tube defects. As the neuropores is called spina bifida with meningomyelcoele. are the last parts of the neural tube to close, defects This may affect sensory and motor innervation at are most likely to occur at its cranial or caudal ends. the level of the lesion, potentially affecting bladder Failure of the neural tube to close caudally affects the and anal continence. spinal cord and the tissues that overlie it, including The neural tube may also fail to close at the cranial the meninges, vertebral bones, muscles and skin. end, causing abnormal brain and calvarial bone Spina bifida (from the Latin for ‘split spine’) is a development. condition in which vertebrae fail to form completely. The brain may be partly outside the skull It may manifest in different degrees of severity. (exencephaly) or the forebrain may fail to develop Spina bifida occulta is the least severe form with a entirely (anencephaly). Exencephaly may precede small gap in one or more vertebrae in the region of anencephaly as the extruded brain tissue L5–S1 often causing little or no symptoms. An degenerates. Anencephaly is incompatible with life. unusual tuft of hair may be present in this region of the back. The incidence of neural tube defects is reduced by folic acid supplements in the diet, but as Spina bifida meningocoele is a failure of vertebrae to neurulation occurs during the third and fourth fuse that is large enough to allow the protrusion of the weeks it should be considered early in pregnancy meninges of the spinal cord externally or when trying to conceive. Neural crest cell derivatives Melanocytes (skin) Thymus (immune system) Dermis, some adipose tissue and smooth Odontoblasts (teeth) muscle of the neck and face (skin) Conotruncal septum (heart) Neurons (dorsal root ganglia) Semilunar valves (heart) Neurons (sympathetic ganglia) Connective tissue and smooth Neurons (ciliary ganglion) muscle of the great arteries (aorta, pulmonary trunk) Neurons (cranial sensory V, VII, maybe VIII, Neuroglial cells (central nervous IX, X) system) Schwann cells (nervous system) Parafollicular cells (thyroid gland) Adrenomedullary cells (adrenal glands) Glomus type I cells (carotid body) Enteric nervous system (gastrointestinal tract, Connective tissue of various parasympathetic nervous system) glands (salivary, thymus, thyroid, Craniofacial cartilage and bones pituitary, lacrimal glands) (musculoskeletal) Corneal endothelium, stroma Bones of the middle ear (musculoskeletal) (eye) Clinical relevance Neural crest cells are important in various areas of An abnormality of migration of neural embryological development, and they must migrate crest cells into the pharyngeal arches in a very organised manner to complete this can lead to improper development of development.. Sometimes, neural crest cells do not the parathyroid glands, thymus, facial migrate to their intended destinations. For example, a skeleton, heart, aorta and pulmonary deficiency in the number of neural crest cells available to form mesenchyme in the developing face trunk. This is 22q11.2 deletion can cause cleft lip and cleft palate. syndrome or DiGeorge syndrome(also known as CATCH22 syndrome). Albinism may be caused by a failure of neural crest Congenital defects vary between cell migration but is more likely to be caused by a defect in the melanin production mechanism. patients with DiGeorge syndrome but it However, pigmentation anomalies are apparent in is likely that they will suffer patients with Waardenburg syndrome, such as eyes hypocalcaemia, a cleft palate, a of different colours, a patch of white hair or patches conotruncal defect such as a ventricular of hypopigmentation of skin. Waardenburg septal defect or tetralogy of Fallot, syndrome is associated with an increased risk of recurrent infections, renal problems and hearing loss, facial features such as a broad, high learning difficulties. These varied nasal root and cleft lip or palate. structures are linked by their Gene mutations of one of at least four genes can development from neural crest cells cause Waardenburg syndrome, including Pax3, a and pharyngeal arches. gene involved in controlling neural crest cell Clinical relevance Neural crest cells are important in various areas of embryological development, and they must migrate in a very organised manner to complete this development.. Sometimes, neural crest cells do not migrate to their intended destinations. For example, a deficiency in the number of neural crest cells available to form mesenchyme in the developing face can cause cleft lip and cleft palate. Albinism may be caused by a failure of neural crest cell migration but is more likely to be caused by a defect in the melanin production mechanism. However, pigmentation anomalies are apparent in patients with Waardenburg syndrome, such as eyes of different colours, a patch of white hair or patches of hypopigmentation of skin. Waardenburg syndrome is associated with an increased risk of hearing loss, facial features such as a broad, high nasal root and cleft lip or palate. Gene mutations of one of at least four genes can cause Waardenburg syndrome, including Pax3, a gene involved in controlling neural crest cell differentiation. Clinical relevance An abnormality of migration of neural crest cells into the pharyngeal arches can lead to improper development of the parathyroid glands, thymus, facial skeleton, heart, aorta and pulmonary trunk. This is 22q11.2 deletion syndrome or DiGeorge syndrome(also known as CATCH22 syndrome). Congenital defects vary between patients with DiGeorge syndrome but it is likely that they will suffer hypocalcaemia, a cleft palate, a conotruncal defect such as a ventricular septal defect or tetralogy of Fallot, recurrent infections, renal problems and learning difficulties. These varied structures are linked by their development from neural crest cells and pharyngeal arches. Time period: day 21 to week 8: Body cavities From a tightly packed, flat trilaminar disc of cells the body cavities must form. This is initiated around 21 days in the lateral plate mesoderm, which splits into splanchnic and somatic divisions. Between these mesodermal divisions vacuoles form and merge creating a U-shaped cavity in the embryo. This is the intraembryonic cavity and initially has open communication with the extra-embryonic cavity (or chorionic cavity). When the embryo folds the connection with the chorionic cavity is lost resulting in a cavity from the pelvic region to the thoracic region of the embryo. Of the two layers of lateral plate mesoderm that divided, a somatic layer lines the intra-embryonic cavity and a splanchnic layer covers the viscera. The septum transversum divides the cavity into two: the thoracic and abdominal (peritoneal) cavities. The division is not complete and there remains communication between these cavities through the pericardioperitoneal canals  Membranes develop at either end of these canals. These membranes separate the thoracic cavity into the pericardial cavity and pleural cavities and are called pleuropericardial folds. The folds carry the phrenic nerves and common cardinal veins and as the position of the heart changes inferiorly, the folds fuse. The pleuropericardial folds will form the fibrous pericardium.