Embryology PDF

lOMoARcPSD|44175252 Horizontal/transverse - Distal = further - Adduction = from where limb moving closer to - Superior/inferior...

lOMoARcPSD|44175252 Horizontal/transverse - Distal = further - Adduction = from where limb moving closer to - Superior/inferior Anterior attaches to body midline halves (ventral)/posterior (dorsal) external/internal medial/lateral rotation = longitudinal axis - Anterior = front - External = - Posterior = back outside - Medial/internal - Internal = inside rotation = rotating inwards Ventral/dorsal - Lateral/external - Ventral = front rotation = - Dorsal = back rotating outwards EMBRYOLOGY Congenital disorder: - Condition present at/before birth regardless of cause - Occurs in 3% of live births - E.g. o Orofacial clefts (lip, palate) 1:1000 o Trisomy 21 (Down) 1:700-900 (1:380 if early termination and death also counted) Stages of Embryology Conceptus Fertilization — week 2 Embryo Week 3 — week 8 Foetus 3rd month Stages of Early Development 1. Ovulation (end of 2nd week) = Secondary oocyte is released from the ovary and is swept into the oviduct 2. Fertilization (end of 2nd week) = a single sperm penetrates oocyte and sperm and egg fuse to form a zygote 3. Cleavage = Zygote undergoes rapid mitotic cell division moving along oviduct becoming a pre- embryo 4. Morula (day 4) = solid ball of cells entering the uterus 5. Blastocyst (day 6) = hollow ball of cells with a fluid filled cavity, freed from the zona pellucida and can increase in size 6. Implantation = blastocyst attaches to the endometrium and 3 germ layers form Blastocyst - Initially contains 2 types of cells: o Trophoblast = outer epithelial layer, goes on to form extra-embryonic structures o Embryoblast/inner cell mass = goes on to form embryo - Between 5 and 10 days, blastocysts implants into uterine wall o Ensures implantation, differentiation, cavity formation - Blastocyst then goes on to form 2 germ layers from the splitting of the inner cell mass into: o Epiblast = upper o Hypoblast = lower  lOMoARcPSD|44175252 - Between these 2 germ layers is the embryonic disc, which goes on to form the embryo Gastrulation - Process of the blastula becoming a gastrula as it forms 3 germ layers: ectoderm, mesoderm, endoderm - Formation of primitive streak: defines all major body axes - gives rise to distinct tissues in adults - On upper surface of bilaminar disc (on epiblast) a line of thickened cells appear = primitive streak - Begins with the formation of the primitive streak on the dorsal side - Primitive streak o Line of thickened cells which appear on the epiblast o Defines all major body axes - Primitive streak invaginates to form the primitive groove - Cells migrate through the primitive groove to form the 3 germ layers: o First cells which migrate replace the hypoblast and form the endoderm o Next cells migrate into the space between the epiblast and endoderm to form the mesoderm o Remaining epiblast cells form the ectoderm - As cells migrate through the primitive streak, they distribute evenly  lOMoARcPSD|44175252 Embryonic body axes Adult body axes Primitive node o Located at the end of the primitive streak o Fluid filled o Sets up left-right asymmetry o Rotating cilia inside the node cause leftward fluid flow o How does this leftward fluid flow break symmetry and indicate to the cells which side they’re on? o Morphogen hypothesis = fluid pushed to the left has molecules in it which bind to receptors and signal to cells which side they’re on o Node vesicular parcel hypothesis = molecules in the fluid are in vesicles o Two cilia hypothesis = cilia at the bottom of the node rotate, while cilia at the top are nonmotile and sense motion to signal to the cells which side they’re on o Confusion of what side of body axes cells are on can cause sinus inverts disorders o Situs invertus (1:8000) § Organs are mirrored form their normal position § Only some organs are partial: Situs ambiguous or heterotaxies § Often associated with other problems, especially heart defects  lOMoARcPSD|44175252 Summary of early development ECTODERM Neurulation is the process by which the neural plate and neural tube are formed Neural Plate - Formation of the neural plate is induced by the notochord - Located from the cranial end to primitive node - Ectodermal cells above the notochord differentiate into a thick plate of pseudostratified epithelial cells - This forms the neural plate Neural Tube - Extension and invagination of the neural plate cases the formation of a neural groove - Groove closes to form neural tube Neural Crest - Located where neural folds meet - Once the tube is closed, cells undergo epithelial à mesenchymal transition and migrate - Neural crest cells give rise to: o Dorsal root ganglia o Enteric ganglia o Schwann cells o Melanocytes o Parasympathetic and sympathetic ganglia o Muscle, cartilage and bone of the skull, face, jaw, pharynx and dentine  lOMoARcPSD|44175252 Segmentation of the Neural Tube - Cranial end of the neural tube forms vesicles, which gives rise to the brain - Remainder forms the spinal cord - The patterning of this segmentation is regulated by Hox genes: o Order and location of gene/s on the chromosome predicts the pattern of expression in the embryo o Areas of the CNS where the gene is expressed corresponds to its location on the chromosome Development of Skin - Epidermis arises from ectoderm that is colonized by melanocytes (neural crest cells) and Langerhans cells (immune cells from bone marrow) - Dermis in the face arises from neural crest cells too, and therefore is ectodermal BODY FOLDING o End of 3rd week: embryo is flat, ovoid, trilaminar disc Fourth week - Embryo growth is rapid, especially in length - Folding initiates to generate body form - Driven by different growth rates (embryonic disc and amnion grow faster than the yolk sac) - Yolk sac = almost no growth - Folding occurs in the cranial-caudal and lateral axes  lOMoARcPSD|44175252 MESODERM Mesoderm differentiates through body folding: 1. Paraxial mesoderm 2. Intermediate mesoderm 3. Lateral mesoderm Notochord - Cartilage-like transient structure - Important for the induction of other organs (e.g. neural tube) - Cranial-midline extension of the primitive node to form a hollow tube - Tube grows in length as cells are added from the primitive node - Primitive streak regresses as the notochord grows (if it doesn’t regress, it causes teratomas)  lOMoARcPSD|44175252 FATE OF MESODERM Paraxial Mesoderm = somatic mesoderm - Located closest to the neural tube - Differentiates into different cells in the head vs in the trunk - In the head, paraxial mesoderm along with neural crest cells form the bone, muscle and connective tissue of the face and skull - In the trunk, paraxial mesoderm forms somites, which gives rise to dermis, muscle and bone Lateral mesoderm: o divided into somatic (parietal) and splanchnic (visceral) o Ventro-lateral body wall (connective tissue, not muscle) o Heart and vasculature o Wall of gut o Bones of the limbs Somitogenesis - Occurs through a mesenchymal à epithelial cell transition - As mesenchymal cells become more organised epithelial cells, somites fissure and close off - Occurs in a cranial à caudal direction, in parallel on both sides of the neural tube  lOMoARcPSD|44175252 - Somites differentiate into: o Epithelial dermamyotomes — which further differentiate into dermatomes (forms dermis) and myotomes (forms muscle) o Mesenchymal sclerotomes § Undergoes a epithelial à mesenchymal transition § Forms the skeletal elements of the trunk - This differentiation is driven by Hox genes Formation of Vertebrae - Each sclerotome splits into cranial and caudal sections (essentially in half) - Spinal nerves grow through to innervate myotomes and dermatomes - Caudal section of one sclerotome fuses with the cranial section of the below sclerotome to form a vertebra Limb Formation - Limbs grow from somites  lOMoARcPSD|44175252 - Form at limb fields and bud off - Mesenchymal cells from lateral plate mesoderm and somites migrate in towards these limb fields - LP mesoderm forms the skeletal elements of the limb, while somites form the muscle and dermis of the limb - Limb segmentation is driven by Hox genes - Digit formation = hands and feet start off as paddles, and digits are sculpted by apoptosis Intermediate Mesoderm - Located between lateral plate and paraxial mesoderm - Forms the urogenital system (kidneys, gonads and associated ducts) Kidneys - Nephric duct (Wolffian Duct) forms in the mesoderm - At the cranial end, tubules form (pronephros) which connect to the nephric duct, but quickly deteriorate - At the caudal end: o Tubules form (mesonephros) which acts as the embryonic kidney o Bud forms out of the nephric duct (uretric bud) which gives rise to the ureter - The end of the uretric bud fuses with metanephric mesenchyme to form the kidney Genital tracts develop from 2 ducts Nephric = mesonephric, wolffian duct Mullerian duct = formed from invagination Mullerian duct (female duct) ➤ oviduct, uterus, upper vagina In females (XX): no SRY, genital ridge develops into ovary, therefore: o No AMH: Mullerian duct develops into oviduct, uterus, upper part of vagina o No testosterone: Wolffian duct disappears Wolffian duct (male duct) ➤ epididymis, vas deferens, seminal vesicles In males (XY): SRY on Y drives genital ridge to develop into testis, which produces: o AMH; degeneration of Mullerian duct o Testosterone: Wolffian duct develops into epididymis, vas deferens, seminal vesicle  lOMoARcPSD|44175252 Gonads - Form at the nephric duct from thickening of the surface of the mesonephros - Gonads develop as the genital ridge, which is a bipotential precursor (can differentiate into ovaries or testes) - SRY gene on the Y chromosome drive differentiation of the gonads into testes - Lack of SRY gene (due to no Y chromosome) causes differentiation into ovaries - Genital tracts run parallel to the mesonephros - All embryos have Wolffian and Mullerian Ducts - If the gonads à testes, testosterone and antimullerian hormone (AMH) cause degeneration of the Mullerian duct, and the Wolffian duct goes on to form the male reproductive tract - If the gonads à ovaries, the Wolffian duct degenerates due to a lack of testosterone, and the Mullerian duct foes on to form the female reproductive tract Lateral Plate Mesoderm - Located furthest from the neural tube - Divides into to somatic (parietal) and splanchnic (visceral) LP mesoderm - Through body folding, splanchnic LP mesoderm is closer to the neural tube than somatic LP mesoderm - Forms the ventrolateral body wall, heart and vasculature, and the gut wall  lOMoARcPSD|44175252 Splanchnic LP Mesoderm forms the circulatory system. Vasculogenesis - De novo assembly of blood vessels - Requires recruitment of mesodermal progenitors to endothelial cells, which then are organised into vessels - Occurs only during embryogenesis - Steps: 1. Endoderm signals to mesoderm, causing mesodermal cells to cluster and form haemangioblasts 2. Haemangioblasts differentiate: - Outer cells form angioblasts - Inner cells form haematopoetic cells 3. Haematopoetic cells go on to form blood cells, while angioblasts go on to form endothelial blood vessels 4. Vessels recruit pericytes that stabilize the vessel, and allow the vessel to contract Angiogenesis - Blood vessel formation from pre-existing vasculature - Occurs during embryogenesis and as an adult - Occurs in a state of hypoxia - Vessels produce a growth factor (VEGF-A) which causes sprouting of endothelial cells of blood vessels towards the GF - Sprouts on adjacent vessels fuse and lumen forms - Pericytes strengthen the vessel  lOMoARcPSD|44175252 Tumour angiogenesis: o When a tumour is too large to survive through diffusion, it will release GF (VEGF-A) causing nearby vessels to sprout o Blood vessels provide the tumour with oxygen, and facilitate metastatic spread Formation of the heart: o Two endocardial tubes fuse in the centre to form the primitive heart tube o The tube has 4 vessels leaving it (go on to form the great vessels) o Heart tube twists and loops, and septum s form to separate the 4 chambers  lOMoARcPSD|44175252 Lymphangiogenesis - Lymphatic system develops from pre-existing veins - Cardinal veins buds towards a GF (VEGF-C) to form lymph sacs - Lymph sacs then form their own vascular system Septum Transversum - Through body folding, some mesodermal cells move under and inwards, essentially cutting the embryo in half, these cells form the septum transversum - Septum transversum separates the coelom into thoracic and abdominal cavities, as it develops into part of the diaphragm - Also forms part of the ventral mesentery of the stomach and duodenum BODY FOLDING Fourth week: o Embryo grows rapidly o Process of folding to generate body form Main force: differential growth of various tissues Embryonic disc and amnion: high growth rate Yolk sac: almost no growth Folding of cranial, caudal and lateral body folds  lOMoARcPSD|44175252 ENDODERM - Important for inducing the formation of mesodermal organs (signal to mesoderm to form certain organs) - Forms the lining of the digestive tract - Body folding: o Lateral folds fuse to complete the gut tube o Exception of where the yolk sac connects o Through body folding, LP mesoderm is recruited to the gut wall (splanchnic lines the gut, while somatic lines the body cavity/coelom - Gut tube is sealed off by 2 membranes, which eventually disappear: o Buccopharyngeal membrane (seals off mouth) o Cloacal membrane (seals off anus) Allantois o Located at the caudal end of the gut tube o Sac-like, blind ending structure o Endodermal, surrounded by blood vessels, which become umbilical arteries and veins o Has a role in gas exchange and excretion in the embryo o Later becomes the urachus (connects the foetal bladder to the yolk sac) Development of the Gut - Primitive gut develops at the beginning of the fourth week - Closed at cranial end: oropharyngeal membrane - Closed at caudal end: cloacal membrane - Primitive gut is closed at both ends - 3 gut regions, defined by their blood supply: o Foregut — supplied by the celiac artery o Midgut — supplies by the superior mesenteric artery o Hindgut — supplied by the inferior mesenteric artery - Patterning is defined by Hox genes  lOMoARcPSD|44175252 Body supply o Foregut from celiac artery o Midgut from superior mesenteric artery o Hindgut from inferior mesenteric artery  lOMoARcPSD|44175252 Regional patterning of the gut tube Development of the Stomach: - Develops from the gut tube - Distal part of the foregut, around middle of the fourth week, slight dilation - Dilation in the distal part of the foregut - Enlarges and broadens ventro-dorsally - Dorsal part grows quicker than ventral part, causing curvature - 2 x 90O rotations clockwise (in different planes): o Dorsal part moves left, ventral part moves right about the dorsal-ventral axis o Stomach bends into a C shape (inferior part rotates superiorly) Development of other endodermal organs - Endodermal thickening results in cells proliferating and bud growth - Continues lengthening and bifurcating results in formation of the lungs, liver, gall bladder and pancreas Development of the Lungs: - Starts from a ventral out-pocketing if the endoderm (respiratory diverticulum) which forms the trachea - Bud grows ventro-caudally - Bifurcates to form the left and right tracheal buds, which will form the bronchi  lOMoARcPSD|44175252 - Tracheal buds bifurcate into secondary bronchial buds, which will form the lung lobes o 3 right secondary bronchial buds o 2 left secondary bronchial buds - Secondary bronchial buds bifurcate into bronchopulmonary segments - 14 more bifurcations result in the formation of terminal bronchioles - Between each branching there is lengthening Gut Tube and Derivatives Gut Tube Proper Derivative Foregut Pharynx, oesophagus, Thyroid, parathyroid, stomach and proximal lungs, liver, gall bladder duodenum and pancreas Midgut Distal duodenum to the proximal ½ of the colon Hindgut Distal ½ of the colon to anus Urinary bladder HEAD STRUCTURES Many skeletal elements of the head are from neural crest cells, not mesoderm. Pharyngeal Arches/Brachial Arches - Human embryo has 4 pairs of pharyngeal arches, from which many head structures are formed - These arches have an outer-covering of ectoderm, and inner-covering od endoderm, and a mesenchymal core, derived from paraxial and LP mesoderm, and neural crest cells - Pharyngeal arches = outer arches - Pharyngeal cleft = ridge between arches - Pharyngeal pouch = inner arches - Each arch has: o Arch specific cranial nerve o Aortic arch artery (splanchnic LP mesoderm derived) o Central cartilaginous elements (neural crest derived) o Striated muscle rudiment (head paraxial mesoderm derived)  lOMoARcPSD|44175252 GERM CELLS Primordial Germ Cells (PGC) - Prior to the differentiation of the 3 germ layers, cells are set aside germ cells (these are PGC) - PGC are the precursors for sperm and eggs - These cells remain pluripotent - Formation of the PGC is initiation by inductive signalling from the cells around them Migration (PGC) - PGC are not specified in the gonads, but rather at the base of the allantois - PGC migrate along the hindgut, through the dorsal mesentery, then split into the left and right genital ridges, where they stop migrating