Lecture 5: Limb Development PDF

Development of Limbs, Integumentary System & Body Cavities Lecture 5 Vrushank Davé, MS/Ph.D. Director, Biotechnology Graduate Program Associate Professor Dept. of Pathology & Cell Biology Dept....

Development of Limbs, Integumentary System & Body Cavities Lecture 5 Vrushank Davé, MS/Ph.D. Director, Biotechnology Graduate Program Associate Professor Dept. of Pathology & Cell Biology Dept. of Molecular Medicine & Oncologic Sciences USF Morsani College of Medicine Office: 813-974-0930 E-mail: [email protected] Part I: Limb Development Learning Objectives: 1. Mechanism driving early establishment of Limb Development 2. Understand the final stages of Limb Development 3. How are Cutaneous Innervation of Limbs established? 4. Study the Blood Supply of Limbs 5. Comprehend the Major Birth Defects of Limbs 6. Summary of Limb Development Four Cellular Processes that promote Limb Formation fore limbs comeout calier than the hind limbs bu there's abundant well division limbs get sculpted and & separate we fingag - b do apoptosis - wntled need Hig cignaling PAX3 serise pathways 6 asser creimportant for proper of migration limb bed He Early Stages of Limb Development limb buds appear from the which i & body wall conate a Day 28 4 pharyngeal wonesformed S log § By Day 24 (upper limb) & Day 26 (lower limb) buds appears from the day 28 & somatic lateral mesoderm (body wall or parietal wall) forms § Buds have a mesenchyme core + outer epithelial ectoderm § Muscle cells migrate into the bud from the somites. this is internal once made migrates its called a progress the § A(progress zone (PZ) under the tip of the bud has proliferating C proliferate mesenchyme, which elongates the limb buds. He fastest and cases the limbs to more toward § The epithelial Apical Ectodermal Ridge (AER) lies above the PZ & initiates limb bud formation. is form as the mesoderm quotes who the skin § Upper limb buds appear low as the cranial half grows faster. § Upper limb buds form opposite to the caudal cervical segments. § Lower limb buds form opposite to the lumbar/upper sacral segments. they're very how of the comitestvatebrae Limb patterning: Regulation by Positional Information: bore madels vede and blood Two developmental fields are formed in the early limb bud: § ANTERIOR: Apical Ectodermal Ridge (AER) at the limb bud tip He internal reahas § POSTERIOR: TWO PZs (Progress Zones)à Proximal PZ & Distal PZ by aggregation/condensation of mesenchymal cells & § AER at the distal tip, induces proliferation of the underlying undifferentiated mesenchyme, elongating the limb bud. § Later, 2 Progress Zones; PZs begin differentiation and condense into the cartilage precursors, initiating limb bone formation § Proximal PZ differentiate into [blood vessels + cartilage bone models] Sand - plates foot plates § Distal PZ (tip) of the limb buds flatten into Hand plates + Foot plates He AER rignal He underlying vnto mewdam to differentiate a urtain fate. then they signal to the difeet proximal merodam to has a fatt Early Embryonic Limb development Day 32–56: Note: Upper limbs develop earlier than the lower limbs. it has 1. Day 44: Mesenchyme in the hand plates condense internally models formed bore cells are to form digital rays, forming fingers b and the undergoing apoptosis 2. Day 48: Footplates develop in the same way. 3. At the tip of each digital ray, the AER induces the mesenchyme to become bone primordia (phalanges). 4. Mesenchyme between the digital rays apoptose, forming fingers & toes by end of week 8. these why we undergoing apoptosis y hands , elbow now apoptosis and arch of multirent enough S I by is y separate Tay↑. there now  - about of proliferation Final Stages of Limb Development in in the so internal Pt is much that itverve arusion He distal ot mesedge look takes meserchipe over He condensing Mesenchymal cellular condensation forms bone models: bore primordia End of 5th Wk (D35): Chondrification centers appear. We formed End of 6th Wk (Day 42): The limb skeleton is cartilaginous End of 7th Wk: Osteogenesis of long bones begins in the primary ossification centers. catilage remains until day She End of 12th Wk: Ossification centers are present in all long bones by week 12 treel be enough orviscation  52 days: Elbows, Knees & Digit Formation end of 8 weeks 52 days: digits separated -- Fingers separate due to web-apoptosis for forelimbs but not hindlimbs -- Feet are fan shaped & toes are fused 56 days: 56 days: -- Elbows , Knees & separated hand & feet digits visible. -- Embryo becomes a fetus, and the limb & M position changes day 56 tree demoration separated now - see where - of elbow can you knees und one where the elbows are Upper & Lower Limb Rotation is Complete by Day 56 (end of 8th-week) § Upper limbs rotate laterally by 90 degrees: Elbows come to point Dorsally & Caudally § Lower limbs rotate medially by 90 degrees; Knees come to point Ventrally & Cranially knees point cranialy elbaus point caudally I S Dermatome Patterns & Cutaneous Innervation of Limbs 5th Week me & See 1. Motor & Sensory Spinal axons grow in the dorsal & ventral muscles of the limb buds. - & mites S 2. Neural crest cells give rise to Schwann cells, & myelin sheath surround motor/sensory nerve fibers, makes cone of 14 toot and forming Neurolemma (Sheath of Schwann). we calf t gas He stal I u 3. Every dermatome originates from a single somite & has area of skin innervated by a single spinal nerve & & ↳ 9 C T its spinal ganglion. Cloves between each verlebel ↑ L5 hims He S / for each spiral ganglia you -and Lord pat have a spiral neve calf aes of the 4. Dorsal dermatome…. (preaxial border) § Medial rotation of the lower limb: Original ventral surface of the lower 5. Ventral dermatome…. (postaxial border) limb goes to the back of the adult limb. § L5 and L2: Rotated to the posterior aspect § S1, S2, S3: Rotates to the center at the ventral axis Developing Blood Supply to Upper Limbs: Dorsal Aorta à Intersegmental A. Primary axial A. Anterior interosseous Brachial A. à Common interosseous Posterior interosseous Ulnar A. Radial A. Superficial Palmar Deep Palmar Arch (SPA) Arch (DPA) a lot ofoiling degenerate be there's a lot of 'remodeling "regenerals & S bu Hey remodel Developing Blood Supply to Lower Limbs: Dorsal Aorta à Common Iliac A. àBifurcates into: (1) Primary axial artery à profunda femoris (Deep artery of the thigh) (2) Ext. Iliac à Femoral artery Popliteal artery Posterior Tibial A. Anterior Tibial A. im-§ Fibular (peroneal) A. [center] th § Lateral Planter A. Foot & toe § Medial Planter A. Capillaries Birth Defects of Limbs Week 4- & § D24 -36: Limb defects occur during the most critical period of limb development. Common: 1:500 neonates. datented & § Thalidomide (teratogen) is most potent at 3-5 week stage & causes. Sirenomelia § Amelia: Absence of limbs à Quadruple Amelia: all 4 limbs missing!! (A) (C) § Meromelia: Partial limb formation (B) § Sirenomelia (Mermaid Syndrome): Caudal dysgenesis: lower limbs fused; appears like a mermaid's tail : Exact cause unknown; sporadic! (C) J Clin Neonatol. 2012 Jul;1(3):146-8. NORD: https://rarediseases.org/rare-diseases/sirenomelia/ Split-hand/foot malformations (SHFMs) into e modern happens when AER doesn't signal properly § Bifurcated (forked) hand Fingers missing § Cleft foot § Absence of one or more central digits § Fingers missing (D) § Toes missing (E) Cause: Failure of development of one or more digital rays Toes missing Brachydactyly & Polydactyly Brachydactyly: Shortness of the digits (fingers or toes) due to reduction in the length of the phalanges slubby and S short , -- Dominant inherited trait urved -- Shortness of body or overall short stature Polydactyly: Shows more than five digits on the hands or feet. -- Extra digits are called “supernumerary digits”. -- Dominant inherited trait. Katarina Lehmann et al. PNAS 2003;100:12277-12282 Syndactyly both can be fixed with surgery Syndactyly (2 Types): top but are used at the bottom might be open on. 1. Cutaneous syndactyly: Simple webbing between digits is frequently found in the foot than in the hand. § Cause: Failure of the webs to degenerate between two or more digits due to blockade of cell apoptosis; thus, the digits do not separate. (two arrows on webbing) 2. Osseous syndactyly: Fusion of bones (synostosis): painful § Notches between the digital rays fail to develop & digits do not separate § Seen frequently between the: bore models trse § 3rd & 4th fingers (fore-limb) § 2nd and 3rd toes (hind-limbs)  in growing of the fook S Congenital Clubfoot Talipes equinovarus (Latin talus (ankle) + pes (foot)) or clubfoot is a common birth defect with musculoskeletal deformation (1:1000 births). Cause: Multifactorial inheritance Characteristics: -- Abnormal position of the foot does not allow normal weight bearing. -- The sole of the foot is turned medially, -- The foot is inverted (incurving) -- Seen bilaterally in 50% of cases -- Occurs twice as frequently in males TREATMENT: Casting or taping & physiotherapy Neonate with bilateral talipes equinovarus (clubfeet) will near achive normal structure Observe the hyperextension and incurving of the feet Summary of Limb Development § Limb buds appear 24-28th day of gestation as slight bulges on the ventrolateral body wall. § Upper limb buds develop 2 days ahead of lower limb buds from mesoderm + ectoderm. § The limb buds elongate by proliferation of the mesenchyme. § Cell apoptosis degenerates tissues in the notches between the digital rays. § Limb muscles are derived from mesenchyme (myogenic precursor cells; myoblast) originating in the somites. Myoblast convert to myotubes to form mature muscles. § Myoblasts migrate and form dorsal and ventral muscle masses. Nerves grow into these muscle masses. § Blood vessels in the limb buds arise from the intersegmental arteries. § Most birth defects of the limbs have hereditary influence; many arise as a result of interaction of genetic & environmental factors (multifactorial inheritance). Development of the Integumentary System surface etoderm mesoderm Integumentary System Skin and its appendages that protects the body Cat is don't divds they just get bigger a Objectives: Integumentary System 1. Understand the development of Skin and its Appendages 2. Epidermis: structure, function and formation & derivatives 3. Dermis: structure, function, formation & derivatives 4. Sweat Glands & Sebaceous Glands 5. Mammary Glands: Origin, structure and function 6. Hairs: Origin, formation & structure 7. Nails: Origin, formation & structure Development of the Skin Skin has two layers derived from two different germ layers: § Epidermis: Superficial epithelial tissue derived from surface ectoderm § Dermis: Deeper layer of connective tissue derived from mesoderm Development of the Epidermis in Early Embryo At 4 Weeks: the § for Surface ectoderm of the skin (primordium of the epidermis) § Made of simple cuboidal epithelium unelage Y At 7 Weeks: Simple cuboidal epithelial cells start to proliferate and form TWO layers of made squamous epithelium: periderm and basal layer we made out of ectodom two layus 3out of eutodem First layer: The Periderm: § Undergoes Keratinization à Desquamation (shedding) à à Later, by week 20 complete Exfoliation of peridermal cells forming vernix caseosa Second layer: The Basal layer: § Replaces the periderm and forms the “future stratum germinativum” gemination our ner Successive stages of skin development. At 11 Weeks: § Intermediate layer: several cell layers thick between the basal squamous epithelinn layer & the periderm. equamous § Intermediate layer cells invade the dermis (mesoderm) to ↳ form epidermal ridges, which form future fingerprints grown fast inside the modern estodem and is invading into the NOTE: Moderm is ectoderm unrading into mederm · Chromosomal defects (Down Syndrome): § Abnormal and unique epidermal ridge pattern is used for diagnosis unique hand live and fingerprint pattern Formation & differentiation of Melanoblasts into Melanocytes § Early fetal period: melanoblasts one from neural rest wells - § Melanoblasts move from the dermis mesoderm to the epidermis (ectoderm) § Melanoblasts lodge into dermoepidermal junction and differentiate into melanocytes (pigment-producing cells) between day 40-50 § Melanocytes (Neural Crest Cell derived) with Red heads Black/brown heads distinct melanin pigments invade the dermis.  messderm and come ene from epider mis J § Melanoblasts differentiate into dendritic Melanocytes containing Pigmented Melanin Granules” in Melanosomes, which are taken up by keratinocytes, called Melanokerasomes Greg Glie woud the nucleus T S go who the relatinocytes § Melanocytes reside in epidermis with their dendrites - melanosomes Nu Development of the Multiple Layers of the Epidermis 21st Wk – Neonate: e melano sayatt don't ustes go up § Periderm disappears § Multiple layers of the epidermis are formed by differing stages of keratinization. § At birth all adult epidermis layers are present Mesoderm 1. Stratum corneum (Horney top layer; dead corneocytes) 2. Stratum lucidum (Smooth layer; Eleidin a product of Keratohyalin) & will continue 3. Stratum granulosum (Granular layer) has me making more Abes allo love as we 4. Stratum spinosum (Spinous polyhedral or prickle cell layer) S(Two mesodermal layers of the dermis)top ( 9 M the well from the 5. Stratum basale (Stratum germinativum cell layer) I , wall Formation of the Mature Definitive Epidermis Continuous inductive interactions with the dermis gives rise to two distinct type of epidermis depending on its thickness. Thick skin: Covers the palms of the hands and soles of the feet. -- Has sweat glands only -- No hair follicles or hair -- No arrector muscles of hairs no silglaney -- No sebaceous glands. name (Sweaty palms!) Thin skin: Covers most of the rest of the body & it contains: -- Hair follicles & hair -- Arrector muscles of the hairs -- Sebaceous glands -- Sweat glands Origin & Development of the Dermis 11th week § Mesenchyme underlying the epidermis forms the Dermis § Two origins of the Dermis mesenchyme: o most § Somatic layer of the Lateral mesoderm contributes § Dermatomes of the Somites forms Skin fibroblasts 11th week: Mesenchyme secrete connective tissue, forming: Birth § Collagen fibers § Elastin fibers Sous reticular cases Dermis At birth: the dermis is made up of 2-layers. § The papillary layer § The reticular layer Formation & Function of the Dermal Papillae only the epidermis on top dernis grows fast and pusks between the danis and epidermis interdigitation - stratum germinative is also growing to there's § Between the descending epidermal ridges, the dermis (the papillary layer) interdigitates upward and forms the dermal papillae. Epidermis § Sensory nerve endings invade into the dermal Ep ide papillae. rm al ri dg e § Capillary loops of blood vessels also simultaneously invade the dermis and provide nourishment. Dermis the dermal papillae below the spidermal ridge form the tingerprints  Development of the Hair bulb unvades central portion lees blood does apoplois · unrade ↑ He and forele mederm canty Keratinglyb S b laye only are but invades stay 6 weeks: Hair bud develops but the hair is visible only later, by 20th week. Epidermal cells proliferate inwards, forming hair buds that invade the dermis E 16 wks: The root of the hair bud becomes cup-shaped, forming a hair bulb with a hair the epidermis will invade into shaft multiple layersafterofmission the mesoderm. the central portion will do cavity When apoptosis happens, the apoptosis and form a als die but the. 16 wks: The hair bulb gets filled by Keratin stays mesenchymal “hair papilla”. 6 He keratin gets getter and bors ahai migrating melcounts memounts will go the more you have the int He hai & how daller the hair papilla and S a hair shaft Hair & Sebaceous gland 16 Wks: Central epithelial cells in the hair bulb grows Hair shafts withn & 20 Wks: Hair shaft invades upwards in the sproduced epidermal des epidermis and “protrudes” out of the skin 20 Wks: Peripheral hair bulb cells form the epidermal/dermal root sheath, forming secondary epithelial layer / muscle layer). Laterally: the cells of the epithelial root derived from sheath proliferate to form a sebaceous the dermisand gland bud that produces oily Sebum. forms a muscle dermis layer has first hair fors by week to - / fat cells Development of the Hair & arrector pili muscle Mesenchymal cells surrounding the lower shaft differentiate into dermal root sheath. Arrector pili muscle differentiates from the dermal root sheet mesenchyme For goose bumps For sebum secretion Melanoblasts migrate into the hair bulb & differentiate into melanocytes. Development of the apoptosis so ahollow Sweat Glands itLong stute 20th wk lands I sweak intoG Invade machinge S the 16th wk Sweat glands develop by ~20th wk. 16 Week: Solid growth of epidermal cells invades the dermis 20th Week: Epidermal Terminus coils & body of the gland is formed Apoptosis of the central cells form the lumen of the gland àSweat duct Peripheral epithelial cells of the sweat duct differentiate into 2 types: 1. Secretory cells (sweat) Myoepithelial cell Coiled-coil region 7 2. Contractile myoepithelial cell vone from epidems s freule from superficial cutoderm. Development of the Mammary Glands Mammary glands are modified & highly specialized types of sweat glands. By 4th wk Mammary Crests (ridges) develop along each side of the ventral surface of the embryo. I - Mammary Crests spans the axillary region (armpit) to the inguinal region The Crest regress in most locations & proliferate around pectoral muscles alpopti under e top region Development of the Mammary Glands 12th Week to birth: state germinatin dow goes -T § Down-growth of epithelial tissue continues to proliferate into 16-24 solid out-buddings which give rise to the lactiferous ducts (milk producing) § Surrounding mesenchyme forms: § Fibrous connective tissue § Fat or adipose tissue of the mammary gland all apoptore I formy a cavity ne Or vises is § Epithelial lactiferous ducts at first open into a small mammary pit. § After birth: Nipples rise from the mammary pits because of proliferation/pushing of the surrounding connective tissue mesenchyme 3 Wbula & strukes tors below the Areola, (melanocyte rich region) surrounds the nipples. milk will be produced here  nail originates from eponychium / Development of the Nails 10th Wk: Toenails and fingernails develop as thickened areas of the epidermis (nail fields) at the tips of the digits. Nail fields extend to the dorsal surface and is surrounded by the lateral nail folds. in Cells from the proximal nail fold grow over the nail field and form keratinized nail plate, the primordium of the nail, which grows toward the tip of the finger. nai where is not diebut attacked By 32 weeks the fingernails formed all cliectly ↓ the skin He eaan (keratinized) By 36 weeks the toenail formed x stay Eponychium (corneal layer of epidermis; proximal cuticle) thatnail plate for Hyponychium (skin under the free margin of the nail) Mavacademy (Switzerland)  Part-III Development of the Body Cavities, Mesenteries, & Diaphragm 2 untembryOn - codon  Five Adult Body Cavities 1 2 3 Five Adult Body Cavities: 1. Cranial cavity 2. Vertebral cavity Dorsal cavity 3. Thoracic cavity 4. Abdominal cavity Ventral 4 5. Pelvic cavity cavity 5 Learning Objectives 1. Origin & Division of the Embryonic Body Cavities 2. Mesenteries derived from mesoderm surround the organs 3. Development of the Diaphragm & Septum Transversum 4. Pleuro-peritoneal Membranes 5. Dorsal Mesentery of Esophagus 6. Muscular Ingrowth from Lateral Body Walls 7. Positional Changes and Innervation of Diaphragm 8. Birth defects due to aberrant formation of the diaphragm  Development of the intraembryonic cavity § Day 20: Vacuoles formed in the Lateral mesoderm lamme te hom in S § Day 21: U- or Horse-shoe-shaped body cavity forms in untraembryonic I the lateral mesoderm in a flat trilaminar disc meerdem lones > - from the splitting of He § FLAT EMBRYO splits àU-shaped cavity (Intraembryonic lateral S Coelom) surrounded by two layers: mederm - 22 will amnion A - develop neefrom cardiac -S somatoplane Lateral mesoderm mesoderm zurands the roof S amnios floor Two Layers of the Developing Body Cavities: Two layers: -- Visceral layer – Covers organs -- Parietal layer – Lines the body wall & attached to lung Serous membranes (inner/outer) (Single mesothelial cell layer) Pleura Pericardium Peritoneum Perineum *mesothelium is the just lyer that projects S an organ Serous membranes: Functions to preclude adhesions among organs so that organs can grow & move freely to be Frees netline vineral on the the positioned & sculpted. side and on side pactal Continuity of Intraembryonic & Extra Embryonic Cavity at lateral edges this cancel is inside the embryo but it also goes outside exteembryonic mesderm S intoHe & Chario1 & red is ↳ extrevembryonic meesderm 2. diret communication belved the 2 in early stages S Formation of the Pericardial Cavity Crucial to head - & now brun T cranial to 22 Intra- & Extraembryonic Coelom, Amniotic folds, Chorion & the Yolk Sac intraembryonic welor communicates w the. extraembryonic welom , which fors the choion. Sagittal Sections interm bryonic trucking - D inside Sif He cardiac coalom embryo b extraembryonic t -- all He at this poul Ipoblas alle have come down and He form chorion - Formation of the Dorsal Mesentery & Ventral Mesentery Inver wall of the amnion S is splaichnophare § Coelom is lined by the mesothelium (serous membrane) 4 derived from the: § Somatic mesoderm (inner lining of the parietal layer) - § Splanchnic mesoderm (outer lining of the visceral layer) · § Junction of the somatic (parietal) & splanchnic (visceral) layers of the mesoderm forms: sinlestres M § Dorsally à Dorsal Mesentery held by dosal resentery § Ventrally à Ventral Mesentery He doe mesenting is more muscular is it for than the ventral resentary bu muscular the body wall Formation of the Dorsal and Ventral Mesenteries these louds are the ling bud , hier bud and panueatic land. 1. Descending amnion closes intra / extra-embryonic annutic ~ communication between two coeloms (arrows). callby 2. The arrows in Fig. F indicate the junction of the somatic & splanchnic layers of mesoderm. 3. Somatic mesoderm forms the parietal-peritoneum lining 3 the abdominal wall. O 4. Splanchnic mesoderm forms the visceral-peritoneum covering the organs. Ex oelo c tra m 5. Disappearance of the ventral mesentery & formation of -em bry the ventral body wall (F). on ic 6. Septum transversum moves dorsally and begins to split S the thoracic and abdominal cavities now that the amnion has closed in like this GG His L communication between the intra and disappears. there's no extraembryonic welom. Now there's no open communication w. the choice Embryo in 3-D with Defined Canals & Cavities convection between pericordial and carity peritoreal carily gut tibe goes between a the 2 cavities E coextra- lomemb r yon ic I hasn't demacated t peritoneum is  this has to lift Pericardioperitoneal canals: up I , Cranial folding brings the pericardial cavity to the ventral side of the foregut. The pericardioperitoneal canals: has to uftup to connect -- Arise from the dorsal wall of the pericardial cavity with He -- Pass on each side of the foregut peritored culty that over lifted conal -- Lie dorsal to septum transversum up is He pericord"operitoc -- Caudally, open into the peritoneal cavity Transvers section to understand the origin and position of pericardioperitoneal canals & the septum transversum padxial comiles parxial 6 somites. Notochord dorsal auti this is the -& J J that is P at lifted up. Dorsal mesentery: Pathway for blood vessels, nerves & lymphatics to reach the Gut Tube connected to He urdian carity & 5 week Embryo * vontal If it was the heart mesentery liver only attached it's called dorsal resocardin to the mesentery & ventral I inteste attached to mesoderm- dosul mesently Pathway for blood vessels 1. Celiac arterial trunk (foregut) 2. Superior mesenteric artery (midgut) liver is still part of the it's still Gregut and S 3. Inferior mesenteric artery (hindgut) attached to the body wall. Embryonic Cavities in a 5-week Embryo Midgut: Umbilical cord is attached to the mid-gut. Peritoneal cavities remain separated. directcomunication between He 2 lateralities Peritorial now there's only dosel No messen kely - ventral resentery Hindgut: Peritoneal cavity is continuous  - Formation of the Pleuropericardial folds & Pericardioperitoneal canals At 4 Weeks: Pleuropericardial folds are formed Pericardio-peritoneal canals forms & O O / reated when He bodywall the septum transversum incompletely starts to invade inside the coming from crity bode wall stats to golaterally divides the cavity into two: this region iswall. and medially. Ne body body wal Thoracic cavity Abdominal (peritoneal) cavity starts going that'll. medially Primordial Plural Cavity forms demarcate He pleural carity. Pleuropericardial folds separate the thoracic cavity: At 5 Weeks when the plus pencardial Hold S rise , they'll S demarcate the Two distinct cavities are evident: pleural cavity § Pericardial cavity common cardinal veins § Pleural cavities phrenic nerves & > - Pleuropericardial folds carry the phrenic nerves ↓ & common cardinal veins heart descends to that plunpericidal fold confuse Heart moves inferiorly for the Pleuropericardial neut isolated from placral curity folds to fuse The pleuropericardial folds then forms the fibrous pericardium. Embryology at a Glance, 2nd ed. Separation/formation of the pleural & the pericardial cavities & mediastinum § LUNGS grow inferiorly & expands the pleural cavities. § HEART moves inferiorly be you want lutral peropariol a § Pleuropericardial folds fuse to form fibrous pericardium, isolating the pericardial cavity When the lungs go down they split the wal body lung and de 5 weeks: Pericardio-peritoneal canals & the protected by 2 layers pericardial cavity are continuous (arrows). visivel carity wall) S t way 6 weeks: Lung grows & the pleural cavities expand into the body wall & splits the somatic mesoderm (arrows). Inserte pericardium is fibrous be it's coming from the body was 7 weeks: Pleural cavities expand ventrally around the heart. Pleuropericardial folds fuse medially, ventral to esophagus. 7 weeks 8 weeks: Lungs/pleural cavities expand & split S mesoderm further: (1) Inner fibrous pericardium protecting/isolating be heat now by the heart Prod opencardium -- is te (2) Outer thoracic wall protects the lungs/pleural of es layers cavity. alo protects He newt & has 8 weeks - body wall layer polection S , & pencardium Fibrous visceral and perfordium à Primordial mediastinum (mesenchymal mass), extends from the sternum to the vertebral column. and keeps all He strckes in place  S-shaped cardiac tube Pleuroperitoneal Membranes (folds) & peritoneal cavity: has septum Kansversum in A invaded all the way fold has plun pericordial a the a andup demarcated euns A). Left side view of the primordial body cavities after the removal of the lateral body wall. B) Transverse section through an embryo as shown in figure A. Peritoneal Cavity B -  Development of the Diaphragm The diaphragm develops from 4 components (see Red #1-4): 1. Septum transversum 2. Dorsal mesentery of esophagus 3. Pleuroperitoneal folds 4. Muscular ingrowth from lateral body walls now that pleroperitorial tured you nota body S have He has demarcated S He from ↓ 5 weeks: Unfused pleuroperitoneal folds peritoneum Morx 6 weeks: Migration of myoblasts fuse the pleuro-peritoneal folds with septum transversum & esophageal mesentery 12-weeks: Muscular ingrowth from the body wall (4th component). He last thing that happen in week 12 is development ofthe muscles. Diaphragm in a neonate: Inferior view of the diaphragm of a neonate indicates the embryologic origin of Ceptum a transvers its components. -- Septum transversum forms the Central tendon of diaphragm -- Muscular ingrowth thickens -- Crura of the diaphragm: Two tendinous fines Cixes all the structures (left right & crus; leg like structure), wines S extends below the diaphragm to the vertebral column. all the structures inside & Musculature and Innervation of the Diaphragm phrenic neve from resund Spinal nerves g § After the fusion of the 4 components of the diaphragm, Right phrenic nerve the myoblasts from the pleuroperitineal folds and the lateral body wall invade into the other parts forming the diaphram & give rise to the muscles of the diaphragm. § During development the phrenic nerve descends from spinal nerves (C3, C4, C5) & passes through the pleuropericardial membranes/folds and innervates the muscles of diaphragm Congenital Diaphragmatic Hernia (CDH) or Posterolateral Defect of Diaphragm: CDH occurs commonly through a posterolateral defect in diaphragm (1: 2200 neonates).& considered pretty common Occurs mostly on left side. Left lung hypoplasia is common hole in the diaphragm Herniation of abdominal contents caud by asignificant signaling S b in 56 Abroblast growth factor , intestive will go in here and up ↓. Eventration of Diaphragm: Because of defective musculature development of the diaphragm the abdominal viscera are displaced in the thorax within a pouch of diaphragmatic tissue. no muscular layer N diaphragm is soft and He infestives can push up. Congenital Hiatal Hernia: is Herniation of part of the fetal stomach diaphragm may occur through an excessively large weak esophageal hiatus stomach pushes put of the towards. the ecophages up  Summary of Development of Body Cavities, Mesenteries, & Diaphragm 1. The lateral mesoderm splits to form the intraembryonic coelom (Day 21) 2. Intraembryonic coelom circles cranially to form a U-shaped cavity in the cardiogenic mesoderm by day 28. 3. Cranially, the coelom forms the pericardial cavity and laterally, future pleural and peritoneal cavities. 4. Lateral parts of the intraembryonic coelom move medially towards the ventral aspect and merge to form the peritoneal cavity. 5. The splanchnic layer of mesoderm encloses the primordial gut and suspends it from the dorsal body wall by a double-layered dorsal mesentery (made of splanchnic & somatic layer) 6. Fusion of the caudal pleuroperitoneal folds during formation of the diaphragm separates the pleural cavities from the peritoneal cavity. 7. The diaphragm develops from the (i) septum transversum, (ii) mesentery of the esophagus, (iii) pleuroperitoneal folds & (iv) muscular outgrowth from the body wall. 8. The diaphragm divides the body cavity into thoracic and peritoneal cavities. 9. A birth defect (opening) in the pleuroperitoneal membrane on the left side causes CDH.