Embryology 5 - 4th Week Body Plan PDF

By the 3rd week the anterior-posterior axis and dorsoventral axis are formed. There is a symmetric bilaterality (only visual, they are already molecularly different) and there are three tissue layers. Bilateral symmetry is a big evolutionary step —> this allows efficient motility from place to plac...

By the 3rd week the anterior-posterior axis and dorsoventral axis are formed. There is a symmetric bilaterality (only visual, they are already molecularly different) and there are three tissue layers. Bilateral symmetry is a big evolutionary step —> this allows efficient motility from place to place and thus efficient food seeking, location of mates and predators avoidance (and thus survival) The period that goes from the 4th to the 8th week is the organogenetic period. During this period all major internal and external structures are established. Organ function in this period is minimal except from the cardiovascular system (because nutrients have to be carried around the embryo). The heart starts to beat at around the 21st to 22nd day and can be heard by Doppler ultrasonography during the 5th week. The heartbeat is a consequence of an increased sensibility to electric stimuli and of calcium spikes (which allow contractions). In this period teratogens may cause major abnormalities. Thalidomide (drug used years ago) and birth defects —> thalidomide was not tested on pregnant animals but it was given to pregnant women against nausea and depression. Mothers who had taken this drug gave birth to children with defects in their limbs. If the drug was taken from the 4th week there was a defect in the upper limbs while if was taken from the 5th week defects in the lower limbs were caused At the end of the 4th week the human embryo reaches the phylotypic stage (it looks exactly the same as all the other vertebrates’ embryos) Evolution of the animal body plan: Formation of tissues Symmetry (bilateral) Body cavities (sliding surface due the serosa membrane) Segmentation Two major macroscopic events occurring during 4th week —> folding (delimits the body cavities) and segmentation SEGMENTATION It takes place in the paraxial mesoderm (only in the trunk region, not the head). Segmentation leads  to the formation of somites. Segmentation is one of the earliest morphological manifestations of a complex set of gene expressions that are to determine the basic body plan. The process of segmentation is guided by the expression of Hox genes (which establish the cranio- caudal segmentation along the body axis). Later on they will contribute to organ development. Hox genes have been duplicated over evolution and now exists as four similar groups (labelled A to D) Segmentation becomes less and less evident over time, however our vertebral column reminds us of the somites. The paraxial mesoderm ONLY UNDERGOES SOMITOGENESIS IN THE TRUNK REGION, the head region does not undergo somitogenesis. SOMITOGENESIS It proceeds from rostral to caudal and starts around day 20 in the boundaries between the head and trunk region. It is guided by gene expression and opposite gradients of proliferating and differentiating factors. It leads to the formation of somitomers (42-44 pairs, process ends around day 30). The most rostral ones (from 1-7) won’t give rise to somites (they form the mesoderm of branchial arches instead), the more caudal will disappear and in the end we will be left with around 35-37 somites. CLOCK AND WAVEFRONT MODEL FOR SOMITE FORMATION  c tube Aretino peroxide neural acid mesoderm d rostral reciprocal levees Jandal proeigerating factor When retinoic acid (differentiating factor) and FGF8 (fibroblast growing factor 8, proliferating factor) gradients meet a somite is formed. Retinoic acid is more concentrated rostrally while FGF8 is more concentrated caudally and when these two concentrations reach a reciprocal level (wavefront) the paraxial mesoderm gets segmented through a cascade reaction. The wavefront activates some genes belonging to the notch family and which are not always active (they oscillate between a permissive and non permissive state), so for a somite to form the two genes have to be both in the permissive state when the wavefront reaches them During somitogenesis the cells of the mesenchyme have to change their destiny —> mesenchymal- to-epithelial transition Each somite will differentiate into three main territories —> sclerotome (bones, larger one, divided into different domains), dermatome (dermis) and myotome (muscle). The arthrotome is a subdivision of the sclerotome while the syndetome is a subdivision of the myotome different domains stinscierotome wie ensappen tissue connective skeletal muscles  The SCLEROTOME is divided into different domains —> dorsal sclerotome (neural arch and spinous process), ventral sclerotome (vertebral bodies and intervertebral disks), lateral sclerotome (distal ribs and some tendons), central sclerotome (pedicels and ventral parts of neural arches, proximal ribs or transverse processes of vertebrae) and medial sclerotome (meninges and their blood vessels). The arthrotome will give rise to intervertebral disks, vertebral joint surfaces and proximal ribs. Origin of bones —> axial bones (vertebral column) originate from the somites, limb bones form from the lateral plate mesoderm and craniofacial bones originate from the mesoderm of the head and from the neural crest cells (anterior part of the skull, neural crest have migrating properties) eerotomes spine nerves Sclerotomes of the ventral portion will migrate around the notochord and give rise to vertebrae (1 sclerotome forms 2 vertebrae) The notochord then forms the nucleus polposus of intervertebral disks The notochord is important for guiding cells of the ventral sclerotome to form the vertebrae. The MYTOME divides into two subdivisions —>epimere (dorsal) and hypomere (ventral) The epimere gives rise to epaxial muscles (intrinsic muscles of the back, they have their origin and insertion in the vertebral column) The hypomere gives rise to hypaxial muscle (lateral body wall and limbs Origin of limb muscles — > progenitor myogenic cells migrate into the limb bud from the ventral portion of the myotome. From here a ventral muscle mass will be formed (gives rise mainly to flexors, pronators and adductors) and dorsal muscle mass (gives rise mainly to extensors, supinators and abductors). hypomere migrating During the formation of the muscles the innervation takes place too  Some cells of the epaxial myotome are committed to become a certain type of muscle and thus migrate (after dedifferentiating) to a certain place and start proliferating (differentiating in specific cells for specific muscles). Each type of cell is guided by specific molecules. SEGMENTATION OF THE NEURAL TUBE The neural tube adjacent to somites will be divided into functional segments — > spinal cord segments —> each segment of the neural tube innervates the cutaneous territory (dermatome), the muscular territory (myotome) and the bony-tendineous territory (sclerotome) originating from the adjacent somite. DERMATOME Different territories of our body derive from different somites and are innervated by different spinal cord segments Jenna arses FOLDING and FORMATION OF THE BODY CAVITIES The embryonic disk undergoes a process of folding, both laterally and rostro-caudally. Formation of a tube within a tube —> the embryo acquires a tubular structure (formation of the body wall) and then the primary vitelline sack will be engulfed and will give rise to a second tube (the primitive intestine). The intraembryonic coeloms will be incorporated and they will give rise to the internal embryonic cavities, which will then be lined by serosa (serous membrane) Serous membrane —> epithelial membrane made by two layers (1. Mono stratified epithelium called mesothelium 2. Connective tissue). Mesothelium is able to secrete a fluid which is then sustained by the underlying connective tissue. Serosa lines the speanchuicheyer coelomic cavities and the organs located within those cavities. Serous membranes are a sort of bag with an internal layer (mesothelium) and an external one (connective tissue). The parietal layer layer somatic lines the walls of the body cavity while the visceral layer lines the organs. Between these two layers there is the serous space (fluid-filled) FORMATION OF THE INTRAEMBRYONIC COELOM, why is it important? Very important evolutionary step. Most tripoblastic animals have a fluid-filled space somewhere between the body wall and the gut which can provide numerous functional advantages Advantages of an internal cavity lined by serosa: Organs that are formed inside a coelom can move freely, grow and develop independently of the body wall while fluid cushions and protects them from shocks (es: peristalsis of the gut doesn’t affect the body wall, otherwise the whole body would move during digestion). They allow the development of a longer and larger digestive tract for storage of food, and for a longer exposure to digestive enzyme (if the intestine was smaller we would have to eat way more frequently). Movements of the body wall during locomotion do not distort the internal organs Organs can be attached to each other so that they can be suspended in a particular order while still being able to move freely within the cavity. While the embryo grows the organs have to be moved around but at the same time they have to maintain their reciprocal relationship Larger gonads (more space) and thus more gametes Space for growth of new members of the species inside the maternal body. Formation of an efficient circulatory system A true coelom is the cavity that forms within the mesoderm. Splitting of the lateral plate mesoderm gives rise to an intraembryonic coelom delimited by a parietal (somatic) and a visceral (splanchnic) layer. The parietal layer + the overlying ectoderm form the somatopleura (will form the body wall) The visceral layer + the underlying endoderm form the splanchnopleura (will form the embryonic gut) noserose oneactual aecom within cavity themesomerm 8 mesenteries The intrambryonic coelom communicates with the extraembryonic coelom in just one place —> central region of the embryo (they only communicate for a little amount of time). The intrambryonic coelom has a horseshoe shape. Its rostral part will become the future pericardial cavity (where the primary heart field formed) while the limbs will become the pericardio-peritoneal canals and peritoneal cavity. The distal portion of the limbs communicates with the extraembryonic spaces Early development of the heart (it starts to beat by the 22nd day of gestation) Septum transversum —> region of thick mesoderm rostral to the heart e macrame tube ante The cluster of cells of the primary intreemmmonic cream heart field form two tubes called a endocardial heart tubes. On the side of these tubes the endooraiae hearttube intraembryonic coelom will form the pericardial cavities. With folding the tubes will come together and fuse into one single tube During development there are 2 aorte called dorsal aorte. The endocardial tubes then connect to the system of aorte. Allantois —> extension of the yolk sack in the body stalk (which suspended the sacks in the chorionic cavity). In humans the allantois isn’t very important functionally but in oviparous animals it forms an actual organ.  nametobe FOLDING Here the embryo is stills disc Why does the embryonic disc fold? There is a differential growth of the embryonic structures —> the amniotic sac and the embryonic disc grow vigorously while the yolk sack stays still (we don’t need it anymore). The developing notochord, neural tube and somites stiffen and make the dorsal axis of the embryo harder. Most of the folding is in fact concentrated in the thin flexible outer rim of the disc. The cranial, caudal and lateral margins of the disc fold completely under the dorsal axial structures and give rise to the ventral surface of the body. This way, the trilaminar disc becomes a cylindrical embryo. Folding takes place on the medial/sagittal plane (longitudinal folds) and on the horizontal/transverse plane (lateral folds). Folds come together in the region where the future umbilicus will be LATERAL FOLDING —> it takes place thanks to the folding of the amniotic sac The amniotic sac starts folding and it goes around the embryonic disc bringing the lateral plate mesoderm and the intraembryonic coelom aeen down. The vitelline sack elongates and gets incorporated in the going w e down ras embryo and surrounded by endoderm forming the primitive intestinal tube (just part of it, the rest remains outside and eventually degenerates). The splanchnic mesoderm (visceral layer) surrounds the gut tube while the somatic mesoderm (parietal layer) forms the body wall. The two serosa layers line the intrambryonic coelom. Initially organs are suspended in the coelomatic cavity thanks a dorsal and a ventral mesentery. The dorsal econnection between evmeine saw eintestine era tube mesentery contains vessels and asmenowe nerves directed to the viscera while the amnionsac envelopes the ventral mesentery degenerates the wary ocompletely (except from the region of the future stomach) The envelopment of the body of the embryo by the amniotic sac is complete in the rostral and caudal region. It only remains incomplete in the umbilical region where there is communication between the extraembryonic coelom and intraembryonic one. FOLDING IN THE HEART TUBES’ REGION —> the two endocardial cavities are joined and they give rise to a single pericardial cavity. FOLDING OF THE MEDIAN PLANE (head fold) —> it takes place because the rostral part of the neural tube grows a lot and starts to fold the embryonic disc ventrally (forming the forebrain). This causes an inversion of 180° of the septum transversum, primordial heart, pericardial coelom and oropharyngeal membrane. This way the septum transversum lies caudally to the heart (it will develop in the tendineous centre of the diaphragm). With the cranial folding the primitive foregut (or anterior endodermal pocket) is formed (incorporation of a part of vitelline sac). The foregut lies between the brain and the heart and is separated by the oropharyngeal membrane from the stomodeum (invagination of the ectoderm, it will give rise to our mouth, the oropharyngeal membrane is at its bottom) The foregut will give rise to the oesophagus —> the heart will develop anterior to it The oropharyngeal membrane will then be broken. FOLDING OF THE MEDIAN PLANE (tail region) —> the body stalk becomes ventral and it gets very close to the vitelline duct (narrow part of the yolk sack). The vitelline duct and the body stalk will then get together to form the primordium of the umbilical cord Results of the folding: The primitive intestine is formed (foregut, midgut and hindgut) Midgut —> communicates with the vitelline sac through the vitelline duct. It is closed anteriorly by the oropharyngeal membrane (at the bottom of the stomodeum, future mouth) Hindgut —> the neural tube grows caudally and folds over the cloacal membrane forming the hindgut (or posterior endodermal pocket, which is closed posteriorly by the cloacal membrane (proctodeum, future anal canal)). At this point the primitive streak is caudal to the cloacal membrane and will soon disappear Heart —> ventral to the foregut Septum transversum —> caudal to the heart, future diaphragm Body wall —> incomplete only in the midgut region Body cavities —> lined by serosa Vitelline duct and body stalk —> they come closer to each other and eventually form the umbilical cord The extraembryonic coelom (or chorionic cavity) starts being filled by the growth of the amniotic sac terraryvinionly vinigamen sormentnesiae byte trophoblast ostreaecione The septum transversum is repositioned ventrally and caudal to the heart. The presence of the septum transversum will separate the intraembryonic coelom into a thoracic compartment (pleuro- pericardial cavity) and an abdominal one (peritoneal cavity). The diaphragm is innervated by the phrenic nerve (which is part of the cervical plexus, it is innervated when it’s still very rostral). The pericardial-peritoneal canals allow communication between the thoracic and abdominal cavity and it is only shut when the diaphragm grows completely.  The diaphragm isn’t only formed by the septum transversum (it only forms the central part of it, tendineous centre) Septum transversum + dorsal mesentery + pleuroperitoneal tube + muscular ingrowths of the body wall Posterolateral defects associated to congenital diaphragmatic hernia (CDH) This happens when the pleural cavity and peritoneal cavity continue to communicate even after the formation of the diaphragm. This can lead to the inhibition of development and inflation of one of the lungs. It’s the most common cause of pulmonary hypoplasia (dyspnea). The most common of this herniation takes place on the left side and is called Bochdalek hernia. The Morgagni hernia is rarer and it develops in the anterior part. Polyhydramnios and oligohydramnios may be present (excess or reduced amount of amniotic fluid) PRIMITIVE CIRCULATION The formation of blood vessels begins at the beginning of 3rd week from the mesoderm. The first ones to form are in the extraembryonic mesoderm of the yolk sac, in the body stalk and in the chorion. Two days later vessels are formed in the embryo. Vasculogenesis and angiogenesis are the processes of formation of the primitive circulation The primitive heart is connected to three symmetric network of vessels —> embryonic network (vessels inside of the embryo), vitelline network (inside of the yolk sac) and umbilical network (will form in the umbilical cord, it will connect the embryo with the placenta). Arteries —> they bring blood from the heart to the periphery Veins —> they bring blood from the periphery to the heart Vessels that carry blood to the inflow potion of the cardiac tube —> vitelline veins (poorly oxygenated blood coming from the yolk sac), umbilical veins (richly oxygenated blood coming from the placenta) and cardinal veins (poorly oxygenated blood coming from segmental veins) Blood in the heart is medium oxygenated and it is then pumped in the embryo. At this stage of development the tissues of the embryo only receive medium oxygenated blood. Outflow portion —> the primitive tubular heart is connected to the dorsal aorte via pharyngeal arch arteries. From the dorsal aorte three vessels arise —> vitelline arteries (blood to the yolk sac and to the primitive intestine), umbilical arteries (blood to the placenta) and segmental arterie (perfuse the body of the embryo) aortic gonadic mesoonerm Initially RBC are formed in the mesoderm of the wall of the vitelline sac. Then the liver has a big importance in erythropoiesis The composition of haemoglobin changes during life. Fetal haemoglobin has a annum s higher affinity with oxygen Thalassemia —> heterogenous group of blood disorders affecting the haemoglobin genes and resulting in ineffective erythropoiesis. There are two types: alpha (problems in alpha chains) and beta (problems in beta chains). If all 4 alleles of the alpha gene are changed hydrops fetalis occurs (fetus dies because it accumulates too much water) nontransfusiondependent Vasculogenesis —> ex novo vessel formation from precursor cells of the mesoderm (mesenchymal cells differentiate into epithelia cells, pericytes and smooth muscle cells to form the vessels). Angiogenesis —> formation of new vessels from existing vessels, in adults it is present during the menstrual cycle (reconstruction of the endometrium), wound healing and tumours proliferation Angiogenic mimicry —> some tumours (which need blood to survive and proliferate) trigger the formation of new vessels, which are leaky and facilitate the intravasation and metastasis of tumour cells. Vasculogenic mimicry —> cancer cells organise themselves into vascular-like structures for the obtention of nutrients and oxygen independently of normal blood vessels or angiogenesis