Body System Structures Notes

NOTES NOTES BODY SYSTEM STRUCTURES DEVELOPMENT OF THE SKELETAL SYSTEM osms.it/axial-skeleton-development ▪ Follows gastrulation (AKA formation of ectoderm, mesoderm, endoderm) Axial skeleton ▪ Skull, vertebrae, rib cage, sternum ▪ Derived from mesoderm ▪ Exception: some skull bones come from ectoderm Appendicular skeleton ▪ Pelvic, shoulder girdles; bones in limbs ▪ Derived from mesoderm Pathways of bone development ▪ AKA ossification ▪ Two pathways ▫ Endochondral, intramembranous Figure 29.1 Cross section through an embryo demonstrating ectoderm, mesoderm, and endoderm. Paraxial and lateral plate mesoderm give rise to bones and muscles. Endochondral ossification ▪ Almost all bones ▫ Exceptions: clavicles; parietal, frontal bones of skull; maxilla; mandible; nasal bone; parts of temporal, occipital bones ▪ Hyaline cartilage serves as bone formation model ▫ Mesenchymal cells differentiate into chondrocytes, which form cartilaginous model ▫ Bone develops by replacing cartilage Figure 29.2 Axial and appendicular skeletons. OSMOSIS.ORG 221

Figure 29.3 Endochondral ossification: the primary ossification center is at the center of the cartilage model. Blood vessels enter the primary ossification center, bringing nutrients, osteoblasts, and osteoclasts. Osteoblasts replace chondrocytes at the primary ossification center and replace cartilage with bone. Osteoclasts start to break down the center of bone, which leads to the formation of bone marrow. Intramembranous ossification ▪ Clavicle, flat bones (e.g. parietal bones, mandible) ▪ Bone develops directly on membranous sheaths ▫ Mesenchymal cells differentiate into osteoblasts, secrete osteoid (AKA unmineralized matrix) ▫ Osteoid calcifices after deposition of calcium phosphate DEVELOPMENT OF THE SKULL Neurocranium ▪ Encases brain ▪ Three parts ▫ Membranous neurocranium, cartilaginous neurocranium/ chondrocranium, viscerocranium Figure 29.4 Lateral view of membranous neurocranium. It is composed of the flat bones that form a hard, protective shell around the brain. Membranous neurocranium ▪ Comprises flat bones that cradle brain ▪ AKA cranial vault ▪ Derived from neural crest cells, paraxial mesoderm ▪ Ossifies via intramembranous ossification Cartilaginous neurocranium ▪ AKA chondrocranium ▪ Bones around base of skull ▪ Derived from neural crest cells, paraxial mesoderm; become prechordal, chordal chondrocranium, respectively ▪ Ossifies via endochondral ossification 222 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures Figure 29.5 Lateral view (left) and superior view (right) of bones comprising cartilaginous neurocranium. Viscerocranium ▪ Facial bones ▪ Six pharyngeal arches; facial bones arise from first arch ▫ Dorsal side: maxilla, zygomatic bones, parts of temporal bone ▫ Ventral side: Meckel’s cartilage undergoes intramembranous ossification; becomes mandible ▫ Dorsal tip of mandibular process, second pharyngeal arch → become incus, malleus, stapes Temporary skull structures ▪ Skull bones not fully fused at birth ▫ Allows molding of fetal head during passage through birth canal ▫ Closes by 18 months old, allows brain growth ▪ Sutures: narrow gaps between bone plates filled with fibrous tissues ▪ Fontanelles: wide sutures where > two bones meet ▫ Anterior fontanelle most prominent ▫ Where two parietal, two frontal bones meet Figure 29.6 The viscerocranium arises primarily from the first pharyngeal arch with stapes arising from the second arch. The viscerocranium is composed of the facial bones (illustrated here in a lateral view). Figure 29.7 Lateral and anterior view of the anterior fontanelle where the frontal and parietal bones meet. OSMOSIS.ORG 223

VERTEBRAE, RIBS, & STERNUM Spinal vertebrae ▪ Week 4: develop from somites ▪ Sclerotome portion undergoes resegmentation ▫ Sclerotome cells from cephalic portion of somite fuse with caudal portion of neighboring somite ▪ Sclerotome cells surround notochord, spinal cord; transform into mesenchymal cells ▪ Mesenchymal cells form vertebrae through endochondral ossification ▪ Ribs then emerge from costal facets of thoracic vertebrae Figure 29.9 Relationship between vertebrae, intervertebral discs, spinal cord, and spinal nerves. Figure 29.10 Rib development arises from costal processes of thoracic vertebrae. Figure 29.8 Spinal vertebrae development occurs by resegmentation of somites. Intervertebral discs ▪ Arise from mesenchymal cells between cephalic, caudal sclerotome segment ▪ Notochord enlarges in area of intervertebral disc, contributing to nucleus pulposus ▫ Intervertebral disk formed as nucleus pulposus surrounded by annulus fibrosus ▪ Myotomes bridge intervertebral discs, form vertebral muscles ▪ Primary spinal curves established: thoracic, sacral 224 OSMOSIS.ORG Sternum ▪ Arises from parietal mesoderm layer in anterior body wall ▪ Cartilaginous bars form on either side of midline, fuse ▫ Differentiate into manubrium, main body of sternum, xiphoid process Figure 29.11 Sternum development arises from parietal mesoderm.

Chapter 29 Embryology: Body System Structures DEVELOPMENT OF THE MUSCULAR SYSTEM osms.it/muscular-system-development KEY POINTS ▪ Mesoderm: becomes vast majority of muscles ▪ Paraxial mesoderm: becomes skeletal muscle ▪ Visceral/splanchnic mesoderm: becomes cardiac muscle, some smooth muscle ▪ Ectoderm: becomes remaining smooth muscle DEVELOPMENT OF SKELETAL MUSCLE Mesodermal cells ▪ Form myogenic cells, which undergo mitosis ▪ Form postmitotic myoblasts ▫ Synthesize actin, myosin ▪ Fuse, form multinucleated myotubes ▫ Myotubes synthesize actin, myosin, troponin, tropomyosin, other muscle proteins ▪ Proteins aggregate, form myofibrils (AKA muscle fibers/cells) Somites ▪ Ventral region of each somite forms sclerotome ▫ AKA bone-forming cells ▪ Upper region of each somite forms dermatome plus two muscle-forming areas ▪ Cells of ventrolateral, dorsomedial lip of somites migrate ventral to dermatome, proliferate there to form dermomyotome ▫ Exception: some cells of ventrolateral lip migrate into parietal mesoderm layer of lateral plate mesoderm; these contribute to abaxial domain, discussed below ▪ Lateral somitic frontier separates somite clusters from parietal mesoderm into two domains ▫ Primaxial domain: consists of somites around neural tube; receives signals for differentiation from notochord, neural tube; forms shoulder, back, intercostal muscles ▫ Abaxial domain: receives signals for differentiation from lateral plate mesoderm; forms infrahyoid, abdominal wall, limb muscles Paraxial mesoderm ▪ Divides into segments, AKA somitomeres, in craniocaudal sequence ▪ Seven somitomeres form head, neck muscles ▫ Contribute to pharyngeal arches’ formation ▪ Remaining somitomeres form 35 pairs of somites for trunk region ▪ Undergo epithelialization ▫ AKA form balls of epithelial cells Figure 29.12 Divisions of mesoderm created by lateral somitic frontier. OSMOSIS.ORG 225

DEVELOPMENT OF CARDIAC MUSCLE ▪ Develops from visceral (i.e. splanchnic) mesoderm surrounding endothelial heart tube ▪ Myoblasts adhere via special attachments, which later become intercalated discs ▪ Patterning of striations forms branch-like lines ▫ Unlike straighter lines of skeletal muscles DEVELOPMENT OF SMOOTH MUSCLE ▪ Paraxial mesoderm cells from first seven somite pairs form smooth muscle of head ▫ Includes tongue, jaw muscles, throat muscles ▫ Develops in response to signals released by neural crest cells ▪ Visceral/splanchnic mesoderm surrounding gut tube → becomes digestive system muscles ▪ Ectoderm → becomes sphincter, dilator muscles of pupils, mammary glands, sweat glands ▪ Proepicardial cells, neural crest cells → becomes smooth muscle of aorta, arteries Figure 29.13 Cross section through an embryo demonstrating the origins of skeletal, cardiac, and smooth muscle. Figure 29.14 Different regions of the somite form different body structures. The myotome is responsible for skeletal muscle formation. 226 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures DEVELOPMENT OF THE LIMBS osms.it/limb-development Limb buds: overview ▪ End of week 4: limb buds visible on ventrolateral body wall ▪ Limb bud structure ▫ Mesenchymal core: forms connective tissue, bones ▫ Myotomes: form muscles ▫ Ectoderm cover: forms epidermis of skin Connective tissue & bones ▪ Development determined by series of interactions between ectoderm, mesenchyme ▪ Ectoderm at the limb apex proliferates, forms apical ectodermal ridge (AER) → induces adjacent mesenchyme to remain undifferentiated, rapidly proliferating cells ▫ AKA undifferentiated zone ▪ Ectoderm further influences mesenchyme ▪ Mesenchyme differentiates into cartilage, muscle; forms three components proximodistally ▫ Stylopod: becomes humerus/femur ▫ Zeugopod: becomes radius/ulna, tibia/ fibula ▫ Autopod: becomes carpals, metacarpals, metatarsals ▪ Week 6: limb bud apexes flatten, become hand, foot plates ▪ Fingers, toes formed via localized apoptosis induced by AER ▫ Separates hand, foot plates into five parts ▪ Mesenchyme underneath differentiates into chondrocytes ▫ Chondrocytes form primary hyaline cartilage models of future bones ▪ As chondrogenesis stops, joint formation induced ▫ Condensed mesenchyme differentiates into dense fibrous tissue (forms articular cartilage, synovial membrane, menisci, ligaments of joint) Limb muscle development ▪ Derived from dorsolateral cells of somites ▫ AKA myotomes ▫ Myotomes from C4-T2 migrate to upper limb ▫ Myotomes from L2-S2 migrate to lower limb ▪ During migration to limbs, myotomes form two compartments ▫ Anterior condensation → flexor, pronator muscles of upper limb; flexor, adductor muscles of lower limb ▫ Posterior condensation → extensor, supinator muscles of upper limb; extensor, abductor muscles of lower limb ▫ Ventral primary branches of spinal nerves, mesenchyme divide; form dorsal, ventral branches to these compartments ▫ Week 7: limbs rotate ▪ Upper limb rotates 90° laterally ▫ Lower limb rotates 90° medially Figure 29.15 Limb muscle development: myotomes migrate to limbs, forming anterior and posterior condensations that are innervated by ventral and dorsal branches of the spinal nerve's primary ventral branches. OSMOSIS.ORG 227

DEVELOPMENT OF THE CARDIOVASCULAR SYSTEM osms.it/cardiovascular-system-development ▪ Begins during week 3 ▪ Mesoderm cells travel through primitive streak to embryo’s head, form horseshoeshaped area with two limbs ▫ AKA primary heart field ▪ Vascular endothelial growth factor (VEGF) signals limbs’ cells to organize into two tubes ▪ Lateral mesoderm splits into somatic, splanchnic layers ▫ Concurrently, primitive pericardial cavity forms lateral to each tube ▪ At inferior end, each endocardial tube connects to vitelline vein stemming from yolk sac ▪ Mesoderm cells also form pair of longitudinal vessels (AKA dorsal aortae) LATERAL FOLDING OF EMBRYO Figure 29.16 Early development of the cardiovascular system starting in week 3. Figure 29.17 Structures formed as a result of lateral folding of the embryo. 228 OSMOSIS.ORG ▪ Embryo folds into cylindrical shape as lateral borders meet at midline ▫ Two endocardial tubes fuse, forming primitive heart tube ▪ Left, right vitelline veins also fuse, forming sinus venosus ▫ AKA inflow tract ▪ Aortae fuse, forming aortic sac ▫ AKA outflow tract ▪ Primitive pericardial cavities fuse around heart tube, forming pericardial cavity ▪ Heart tube remains attached to pericardial cavity by sheet of mesoderm called dorsal mesocardium; heart tube now has two layers (endothelial lining, cardiac myoblasts) ▪ Endothelial lining forms endocardium ▪ Cardiac myoblasts form myocardium ▫ Some myocardial cells in sinus venosus begin to produce rhythmic electrical discharge ▪ Mesenchymal cells of dorsal mesocardium form proepicardial organ ▫ These cells proliferate, migrate over myocardium, form epicardium

Chapter 29 Embryology: Body System Structures CRANIOCAUDAL FOLDING OF EMBRYO ▪ Cylindrical embryo folds down its length, forming shrimp-like shape ▫ Heart pushed toward chest ▪ By week 4: heart tube reaches thorax, circulating blood can be seen travelling through heart tube ▪ Primitive atrium: becomes left, right atria ▪ Primitive ventricle: forms left ventricle ▫ Separated from bulbus cordis by bulboventricular sulcus ▪ Bulbus cordis: forms right ventricle, outflow tracts for both ventricles ▪ Truncus arteriosus: at top of heart tube ▫ Pumps blood through aortic sac into early version of circulatory system LOOPING OF THE HEART TUBE Figure 29.18 Craniocaudal folding of the embryo places heart tube in thorax. PARTITION OF THE HEART TUBE Sections of the heart tube ▪ Sinus venosus: left, right sinus horn bring in blood ▪ Primitive atrium, primitive ventricle separated by atrioventricular sulcus ▪ Heart tube folds into “C” shape ▪ Truncus arteriosus and bulbus cordis move down, to right ▫ Form top portion of “C” ▪ Primitive ventricle bends to right of midline, slightly to front ▫ Forms middle portion of “C” ▪ Primitive atrium, sinus venosus ▫ Form bottom of “C” ▪ Enlarging ventricle moves left ▫ Crosses over midline again, covers primitive atrium ▪ Visceral pericardium attaches to outside of heart, forms epicardium Figure 29.19 Heart tube sections and the structures they become. OSMOSIS.ORG 229

Figure 29.20 During week 4, the heart tube undergoes looping: tube lengthens, walls thicken, and sections move towards appropriate locations to continue development. FURTHER PARTITIONING OF THE HEART ▪ Mesoderm proliferates on anterior, posterior walls of atrioventricular canal ▫ Forms anterior, posterior endocardial cushion ▫ Cushions grow towards each other, fuse ▪ Heart now separated into left, right atrioventricular canals ▪ Endocardial cells proliferate on ventricular side of each canal ▫ These form leaflets of mitral, tricuspid valves ▪ Canals now divided into atria, ventricles Formation of the atria ▪ Crescent-shaped septum primum grows downward between future left, right atria ▫ Opening (AKA ostium primum) remains ▪ Septum primum continues to grow, fuses with endocardial cushion, closes ostium primum completely ▪ Ostium secundum appears in center of septum primum ▪ Septum secundum grows downward just to right of septum primum, covers ostium secundum ▫ Leaves small opening (AKA foramen ovale) ▪ Septum secundum acts as one-way valve, allowing blood flow from left to right atrium ▪ After birth, closure of foramen ovale is facilitated by ▫ ↓ in right atrial pressure due to occlusion of placental circulation ▫ ↑ in left atrial pressure due to ↑ pulmonary venous return 230 OSMOSIS.ORG Formation of ventricles ▪ Muscular ridge of tissue grows upward from apex, fuses with thinner membranous region coming down from endocardial cushions ▫ Forms left, right ventricles ▪ End of week four: cardiac loop starts to take shape of adult heart Figure 29.21 Fusion of the endocardial cushions separates the heart into right and left atrioventricular canals. Figure 29.22 Structures contributing to the formation of the atria and ventricles.

Chapter 29 Embryology: Body System Structures DEVELOPMENT OF THE ARTERIAL SYSTEM Development of the aorta ▪ Starts with division of truncus arteriosus ▪ Two endocardial cushions appear on rightsuperior, left-inferior walls ▪ Cushions grow with spiraling trajectory, wrap around each other ▪ Form aorticopulmonary septum ▫ Divides into root of aorta, pulmonary artery ▫ Semilunar valves develop shortly after DEVELOPMENT OF THE VENOUS SYSTEM ▪ Develops from sinus venosus ▪ Week 4: sinus venosus receives deoxygenated blood from sinus horns, opens in center of primitive atrium ▪ Each horn receives blood from vitelline/ omphalomesenteric veins, umbilical veins, common cardinal veins ▪ Next, sinus venosus becomes asymmetric, shifts to right ▫ Caused by left to right shunts ▪ Right sinus horn enlarges; becomes smooth-walled part of right atrium; forms openings for superior, inferior vena cavas ▪ Left sinus horn shrinks; persists as coronary sinus, oblique vein of left atrium DEVELOPMENT OF THE CONDUCTING SYSTEM Figure 29.23 Anterior view of heart visualizing development of the aorta and pulmonary artery. Arteries of head & neck region, pulmonary arteries ▪ Come from five aortic arches ▪ 1st arch: maxillary artery ▪ 2nd arch: stapedial artery ▪ 3rd arch: two common carotid arteries, part of internal carotid arteries ▪ 4th aortic arch ▫ Left 4th arch: aortic arch ▫ Right 4th arch: right subclavian artery th ▪ 6 arch: pulmonary arteries, ductus arteriosus ▪ Special group of myocardial cells in wall of sinus venosus organize, synchronize their electrical discharge, form pacemaker centers ▫ Cells in wall of sinus venosus: form sinoatrial node ▫ Cells in atrioventricular septum: form atrioventricular node ▫ Cells in interventricular septum: form bundle of His ▫ Rest of ventricular myocardium: form modified cardiac myocytes, which become Purkinje fibers Remaining arteries ▪ Develop mainly from right, left dorsal aortae → fuse during lateral folding, form dorsal aorta ▪ Dorsal aorta sprouts posterolateral arteries; lateral arteries; ventral arteries (AKA vitelline, umbilical) Figure 29.24 Aortic arches and their derivatives. The arches exist from weeks four to six and sprout from aortic sac. OSMOSIS.ORG 231

Figure 29.25 The heart's conducting system. FETAL CIRCULATION osms.it/fetal-circulation KEY POINTS ▪ Placenta: low-resistance circuit, organ of gas exchange ▪ Fetal systemic circulation: low-resistance circuit ▪ Lungs: filled with fluid, hypoxic vasoconstriction ▫ High-resistance circuit, no role in gas exchange ▪ Right side of heart pressure > left side of heart pressure ▪ Ductus venosus, foramen ovale, ductus arteriosus shunt blood away from fetal lungs Pattern of flow ▪ Placenta → umbilical vein → divides into left, right umbilical vein ▪ Left umbilical vein → portal vein → liver → hepatic vein → inferior vena cava → right atrium ▪ Right umbilical vein → ductus venosus (bypasses liver) → inferior vena cava → right atrium ▪ Right atrium → left atrium via foramen ovale ▫ Small amount of blood from right atrium enters right ventricle, pulmonary artery, lungs ▪ Blood shunted from pulmonary artery to aorta by small blood vessel ▫ AKA ductus arteriosus ▪ Aorta → oxygenated blood delivered 232 OSMOSIS.ORG to systemic circulation → right, left common iliac arteries → internal, external iliac arteries → umbilical arteries → deoxygenated blood back to placenta CHANGES AT BIRTH ▪ Pulmonary circulatory pressure ↓ while systemic circulation ↑ ▫ When umbilical cord cut, low-resistance circuit removed → systemic circulation increases ▫ Lung fluid replaced by air as neonate takes first breaths/cries ▫ Oxygen diffuses into blood vessels surrounding alveoli, pulmonary arterioles relax, pulmonary resistance falls, blood flows into lungs ▪ Closing of ductus arteriosus ▫ Pressure changes cause decreased blood flow through ductus arteriosus ▫ Complete closure: 12–24 hours after birth ▫ Physical remnant: ligamentum arteriosum ▪ Closing of foramen ovale ▫ Pressure in right side of heart falls, seals foramen ovale ▫ Physical remnant: fossa ovalis ▪ Umbilical vein forms round ligament of liver ▪ Ductus venosus forms ligamentum venosum of liver

Chapter 29 Embryology: Body System Structures Figure 29.26 The fetal right atrium receives blood from the inferior vena cava (via liver and ductus venosus) and the superior vena cava. OSMOSIS.ORG 233

Figure 29.27 In the fetal circulatory system, blood can travel from the right atrium to the aorta through either the foramen ovale or the ductus arteriosus. The majority of the blood takes the first path from the higher pressure right atrium to the lower pressure left atrium, bypassing the right ventricle entirely. The blood that does flow into the right ventricle is shunted from the high pressure pulmonary artery to the lower pressure aorta through the ductus arteriosus. Figure 29.28 The aorta sends blood to the entire body through its various branches. The interior iliac arteries each give rise to an umbilical artery. These arteries travel alongside the umbilical vein and bring deoxygenated blood back to the placenta, where CO2 is delivered and O2 is picked up. This cycle repeats until birth. 234 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures Figure 29.29 The fetal circulatory adaptations and their physical remnants after birth. The umbilical arteries and vein are surrounded by a substance called Wharton's jelly in the umbilical cord. Once exposed to the cold air, Wharton's jelly shrinks and squeezes the umbilical blood vessels, causing them to wither. The arteries constrict and flatten, and are mostly gone within a few months; only a small portion remains and subsequently function as the superior vesical arteries, which supply blood to either side of the bladder. DEVELOPMENT OF THE RESPIRATORY SYSTEM osms.it/respiratory-system-development KEY POINTS ▪ Week 4: starts developing ▫ Lung bud sprouts from foregut portion of digestive tract ▪ Endoderm, mesoderm: form lower respiratory tract structures ▫ Larynx, trachea, lungs Figure 29.30 Week 4: lung bud sprouts from foregut. OSMOSIS.ORG 235

DEVELOPMENT OF THE LARYNX ▪ Begins as slit between 4 , 6 pharyngeal arches ▪ Endoderm of arches: forms laryngeal epithelium, glands ▪ Mesoderm of arches: forms laryngeal muscles, cartilages ▪ Arches carry the laryngeal branches of vagus nerve ▪ Week 5: laryngeal orifice forms ▫ Laryngeal epithelium turns into laryngeal ventricles, which give rise to vocal cords ▪ Week 6: epiglottis forms ▪ Week 12: laryngeal orifice has adult shape; thyroid, cricoid, arytenoid cartilages th th ▪ Composition of lung bud ▫ Endoderm: gives rise to epithelial, glandular structures of trachea, lungs ▫ Visceral mesoderm: gives rise to muscles, cartilage, connective tissue ▪ Lung bud bifurcates into two bronchial buds Figure 29.33 At the loose end, the lung bud bifurcates into two bronchial buds which give rise to the lungs. STAGES OF LUNG DEVELOPMENT Figure 29.31 The endoderm and mesoderm of the pharyngeal arches contribute to larynx formation. Figure 29.32 Key timing and features in larynx development. DEVELOPMENT OF THE TRACHEA & LUNGS ▪ Week 4: two tracheoesophageal ridges grow towards one another, fuse into septum ▪ Septum divides foregut into two regions ▫ Posterior: esophagus ▫ Anterior: lung bud 236 OSMOSIS.ORG Pseudoglandular stage: weeks 5–16 ▪ Bronchial buds differentiate ▫ Left and right main/primary bronchi ▫ Three lobar/secondary bronchi for right lung lobes, two for left lung lobes ▪ Lobar/secondary bronchi: divide into 10 segmental/tertiary bronchi on right, eight on left ▫ AKA lung segments ▪ Segmental/tertiary bronchi divide repeatedly until 15–25 terminal bronchioles formed ▪ Lungs now consist of simple columnar epithelium Canalicular stage: weeks 16–26 ▪ Terminal bronchioles continue to divide, form respiratory bronchioles ▪ Respiratory bronchiole divides into three to six alveolar ducts ▪ Prominent capillary network forms ▪ Week 24: primitive alveoli appear closer to trachea ▪ Lungs now consist of simple cuboidal epithelium ▫ Unsuitable for gas exchange

Chapter 29 Embryology: Body System Structures Terminal sac stage: week 26–birth ▪ More primitive alveoli form ▪ Epithelial lining of terminal sacs differentiate ▪ Flat cells in direct contact with endothelium of the capillaries ▫ AKA type I pneumocytes, form blood-air barrier ▫ Also includes basement membrane ▪ Pulmonary surfactant produced by large, cuboidal cells ▫ AKA type II pneumocytes Alveolar stage: week 36–8 years old ▪ Terminal sacs partitioned by secondary septae ▪ Number of adult alveoli increase ▫ 0–70 million at birth, 300–400 at eight years old ▪ Number of respiratory bronchioles increases with lung size Figure 29.34 The stages of lung development. OSMOSIS.ORG 237

DEVELOPMENT OF THE GASTROINTESTINAL SYSTEM osms.it/gastrointestinal-system-development Primitive gut tube ▪ Forms during week 3 ▪ Extends from buccopharyngeal membrane to cloacal membrane ▪ Divided into three parts according to arterial supply ▫ Foregut, midgut, hindgut Foregut ▪ Supplied by celiac trunk ▪ Gives rise to superior part of digestive tube ▫ Pharynx to first half of duodenum ▫ Also liver, gallbladder, pancreas Midgut ▪ Supplied by superior mesenteric artery ▪ Briefly, midgut communicates with yolk sac via vitelline duct Hindgut ▪ Supplied by inferior mesenteric artery DERIVATIVES OF THE FOREGUT Pharynx & esophagus ▪ Pharynx develops from 4th, 6th pharyngeal arches ▪ Week 4: tracheoesophageal septum divides foregut below pharynx into two regions ▫ Esophagus: posterior ▫ Lung bud: anterior ▪ Esophageal epithelium, glands derived from foregut endoderm ▫ Epithelium proliferates, initially fills lumen ▫ By week 8: becomes hollow tube via recanalization ▪ Esophageal muscles, adventitia derived from surrounding mesoderm Stomach & duodenum ▪ Begin as small dilation of foregut ▪ Ventral mesogastrium attaches ventral border to anterior body wall ▪ Dorsal mesogastrium attaches dorsal border to posterior body wall ▫ Dorsal border: grows faster, forms greater curvature ▫ Ventral border: lesser curvature ▪ Stomach undergoes 90°, clockwise rotation along its length ▫ Pulls dorsal, ventral mesogastria with it Figure 29.35 The primitive gut tube at week 3, including subdivisions and their blood supplies. 238 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures Figure 29.36 The pharynx and esophagus are derivatives of the foregut. The tracheoesophageal septum divides the foregut into the esophagus posteriorly and the lung bud anteriorly. The esophageal endoderm (epithelium) initially proliferates and fills the lumen, but recanalization is complete by week 8. ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▫ Greater curvature moves to right side of body, lesser curvature to left ▫ Stomach now has anterior, posterior faces Ventral mesogastrium: becomes lesser omentum Dorsal mesogastrium: grows, bends as stomach rotates ▫ Forms cavity (AKA omental bursa) between stomach, posterior body wall Omental bursa: communicates with peritoneal cavity through omental foramen ▫ Omental bursa grows, fills with peritoneal fluid ▫ Develops two projections: upper recess, lower recess Upper recess: extends behind developing liver Lower recess: extends downward over developing intestines ▫ Sheets of dorsal mesogastrium that form lower recess fuse, forming greater omentum Stomach rotates once more on frontal plane ▫ Repositions superior end of stomach ▫ Forms cardiac sphincter, pylorus ▫ Turns duodenum into C-shaped loop, with middle of “C” on right side First two sections of duodenum: derived from last part of foregut Tiny tissue buds on last portion of foregut grow, develop into liver, gallbladder, pancreas Liver & gallbladder ▪ Liver bud, AKA hepatic diverticulum, gives rise to liver, gallbladder, biliary duct system ▫ Forms inside ventral mesogastrium, extends into sheet of mesoderm that separates developing heart from midgut (AKA septum transversum) ▫ Contains mesoderm, endoderm ▪ Foregut endoderm forms hepatocytes ▫ During week 12: hepatocytes start producing bile during mesoderm ▫ Forms Kupffer cells, hematopoietic tissue ▫ During week 6: produce red blood cells ▪ Liver bud divides into two parts ▫ Larger, superior portion: becomes liver ▫ Smaller, inferior part: becomes gallbladder Pancreas ▪ Two pancreatic buds eventually fuse to form entire organ ▫ Dorsal bud: forms tail, body, part of head ▫ Ventral bud: forms most of head ▪ Week 10: begins secreting insulin OSMOSIS.ORG 239

Figure 29.37 Lateral view of the embryo visualizing the stomach and associated structures before any rotation has taken place. The stomach presents as small foregut dilation beneath esophagus. Starting at week 5, the liver grows between the layers of the ventral mesogastrium and the spleen grows between the layers of the dorsal mesogastrium. Figure 29.38 The two rotations events in the development of the stomach. 240 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures Physiologic gut herniation ▪ During rapid gut tube growth, primary intestinal loop herniates through vitelline duct, develops inside umbilical cord ▪ Primary intestinal loop protrudes inside umbilical cord, superior mesenteric artery grows between loop’s two limbs ▫ Cranial limb: initially develops above superior mesenteric artery ▫ Caudal limb: develops below superior mesenteric artery ▪ First, loop rotates 90° counterclockwise around axis of superior mesenteric artery ▫ Moves cranial limb to right side of artery, inferior limb to left ▪ Cranial limb becomes convoluted ▫ Marks future jejunal, ileal anses ▪ Caudal limb develops small dilation ▫ Eventually becomes cecum, appendix ▪ Week 10: loop rotates final 180°, moves into abdominal cavity ▫ Formerly caudal limb now frames developing small intestine loops, becomes ascending colon, right 2⁄3 of transverse colon DERIVATIVES OF THE HINDGUT Figure 29.39 Anterior view: the liver, gallbladder, and pancreas develop from tissue buds at the distal end of the foregut. DERIVATIVES OF THE MIDGUT ▪ Key elements ▪ Parts of small, large intestines derive from midgut ▫ Small intestine: third, fourth sections of duodenum; jejunum; ilium ▫ Large intestine: cecum, appendix, ascending colon, proximal 2⁄3 of transverse colon ▪ Left 1⁄3 of transverse colon, descending colon, sigmoid colon, upper part of anal canal derive from hindgut ▪ Begins after caudal limb of midgut, extends to cloacal membrane ▪ Anal canal’s lower portion derives from primitive anus (AKA proctodeum) ▫ Proctodeum: pit of ectoderm that forms below cloacal membrane ▪ Week 4: Urorectal septum forms ▫ Separates cloaca into anterior urogenital sinus, posterior anal canal; covered by urogenital, anal membranes, respectively ▪ End of week 7: separation completed ▫ Anal membrane ruptures, forming continuous anal canal ▫ Anal canal opens in embryo’s tail-region OSMOSIS.ORG 241

Figure 29.40 The process of physiologic gut herniation. Figure 29.41 Hindgut structures at week 7 when the anal membrane has ruptured to form a continuous anal canal. 242 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures DEVELOPMENT OF THE RENAL SYSTEM osms.it/renal-system-development ▪ Begins in week 4 ▪ Intermediate mesoderm on each side of embryo condenses, forming cylindrical structure (AKA urogenital ridge) ▪ Urogenital ridge runs parallel to future spinal column; has two portions ▫ Genital ridge: becomes gonads ▫ Nephrogenic cord: becomes urinary structures Figure 29.42 Week 4: urogenital ridge formation. ▪ Three structures emerge from nephrogenic cord in cranio-caudal fashion ▫ Pronephros, mesonephros, metanephros Pronephros ▪ Beginning of week 4: arises in neck region ▪ End of week 4: regresses ▪ Does not produce urine ▪ Consists of pronephric duct, nephrotomes ▫ Pronephric duct: tube that runs length of nephrogenic cord ▫ Nephrotomes: chunks of tissue that break off nephrogenic cord Mesonephros ▪ Arises in thoracic, upper lumbar region of nephrogenic cord ▪ Consists of mesonephric duct, mesonephric tubules ▪ Mesonephric duct: develops from pronephric duct ▫ Extends pronephric duct to cloaca ▪ Mesonephric tubules: hollow, S-shaped tubes ▫ Connect to mesonephric duct on one end ▫ On other end, form cup (AKA Bowman’s capsule) around clump of capillaries (AKA glomerulus) ▫ Glomerulus extracts fluid from capillaries, fluid flows down duct, becomes urine, drained through mesonephric duct into cloaca ▫ After week 10, permanent kidneys take over, mesonephros regresses Metanephros ▪ Week 5: develops in pelvic region ▪ Forms permanent kidneys ▪ Intermediate mesoderm near the mesonephric duct differentiates into metanephric mesoderm (AKA metanephric blastema) ▪ This induces mesonephric duct to sprout ureteric bud ▫ Ureteric bud connected mesonephric duct via the ureteric stalk ▪ Ureteric bud lengthens, secretes growth factors ▪ This causes metanephric mesoderm to grow (AKA reciprocal induction) ▪ Ureteric bud grows into metanephric mesoderm ▫ Metanephric mesoderm surrounds end OSMOSIS.ORG 243

Figure 29.43 Locations and components of the pronephros and mesonephros. Figure 29.44 Development of the kidney from the metanephros. of ureteric bud, leaving just ureteric stalk uncovered ▪ Week 6: ureteric stalk lengthens, forms ureter ▪ Weeks 7–8: ureteric bud divides in half, forms renal pelvis ▪ Division continues: two major calyces become minor calyces, then millions of collecting tubules Nephrons ▪ Week 8: start forming ▪ Cells in collecting tubules signal adjacent metanephric mesoderm to form round cell clusters (AKA metanephric vesicles) ▫ Vesicles elongate, bend into S-shaped tube 244 OSMOSIS.ORG ▫ End of tube (AKA distal convoluted tubule) connects with collecting tubules ▫ Other end forms proximal convoluted tubule; becomes Bowman’s capsule, glomerulus ▫ Portion between distal, proximal convoluted tubules lengthens, forms loop of Henle ▪ Week 10: nephrons start producing urine ▪ Initially, kidneys nourished by internal iliac arteries ▪ As permanent kidneys develop, they move up from pelvis to reach upper abdomen ▫ Renal arteries form, lower branches degenerate

Chapter 29 Embryology: Body System Structures Figure 29.45 Nephron development begins at week 8. 1: Metanephric tissue cap signals adjacent metanephric mesoderm to form round cell clusters called metanephric vesicles. 2: Vesicles elongate, curve; end of tube connects with collecting duct. 3: Proximal and distal convoluted tubules (PCT, DCT). 4: Tube lengthens between PCT, DCT → loop of Henle. Figure 29.46 The kidneys are originally nourished by the internal iliac arteries. As kidneys ascend, the aorta forms branches at higher and higher levels to supply them. The renal arteries develop once the kidneys have reached their final position and earlier branches degenerate. OSMOSIS.ORG 245

DEVELOPMENT OF THE BLADDER & URETHRA ▪ Week 4: begins developing ▪ Wall of tissue forms in cloaca (AKA urorectal septum) ▫ Splits cloaca into posterior anal canal, anterior urogenital sinus ▫ Top portion of urogenital sinus forms primitive bladder ▪ Ureters develop from ureteric stalk, open into mesonephric ducts ▫ Drain into bladder ▪ Weeks 5–6: mesonephric ducts get absorbed into bladder ▫ Form vesical trigone (AKA smooth part of bladder) ▪ Middle portion of urogenital sinus forms urethra (female); prostatic, membranous parts of urethra (male) ▪ Bottom portion of urogenital sinus grows towards genital tubercle ▫ Forms clitoris (female), penis (male) Figure 29.47 Week 4: the urorectal septum forms, splitting cloaca (forming urogenital sinus, anal canal). Figure 29.48 Development of the bladder and urethra. 1: Top portion of the urogenital sinus stretches out to form primitive bladder. 2: During weeks 5 and 6, the mesonephric ducts are absorbed into the bladder, forming the smooth part of the bladder wall called the vesical trigone. 3: Outcomes for the middle and bottom portions of the urogenital sinus in individuals who are genetically male and female. 246 OSMOSIS.ORG

Chapter 29 Embryology: Body System Structures DEVELOPMENT OF THE INTEGUMENTARY SYSTEM osms.it/integumentary-system-development DEVELOPMENT OF THE SKIN Epidermis ▪ Derived from single layer of surface ectoderm ▪ In second month: cells divide, forms layer of periderm (AKA epitrichium) ▪ Cells of periderm desquamated during second ½ of prenatal life, form vernix caseosa ▪ Neural crest cells invade epidermis, form melanocytes ▫ Move to keratinocytes in skin, hair bulb ▫ Produce skin, hair pigmentation ▪ Cells in basal layer proliferate, form intermediate zone ▪ By end of fourth month, four layers complete ▫ Basal/germinative layer, spinous layer, granular layer, horny layer ▪ Hair, nails, glands all develop as epidermal proliferations Dermis ▪ Derived from mesenchyme from three sites ▪ Lateral plate mesoderm: produces dermis of limbs, body wall ▪ Paraxial mesoderm: produces dermis of back ▪ Neural crest cells: dermis of neck, face ▪ During third, fourth months, dermis forms many irregular papillary structures (AKA dermal papillae) ▫ Project upward into epidermis ▫ Contain Meissner corpuscles (AKA tactile sensory receptors) Hair ▪ Week 12: hair follicles form from cells of stratum basale ▪ Begins as epidermal proliferation that penetrates into dermis (AKA hair bud) ▪ Hair bud invaginates at terminal end, forming hair papillae ▪ Each hair papilla fills with mesoderm ▫ Vessels, nerves develop ▪ Cells of hair bud’s center become keratinized, forming hair shaft ▪ Peripheral cells form the epithelial hair sheath ▪ Mesenchyme surrounding hair bud forms dermal root sheath, attached arrector pili muscle ▪ By end of third month, first hair appears as lanugo ▫ Begins to shed at term ▪ Sebaceous gland forms from small bud in mesoderm ▫ Secretes sebum Nails ▪ By end of third month, nail fields form from thickenings at tips of digits ▪ Nail fields form nail root through migration ▪ Growth proximal, dorsal to each side of digit ▪ Tissue proliferates around each nail field, forming shallow depression ▪ Epidermis at nail roots differentiates into fingernails, toenails ▫ Reaches tips by ninth month of development Sweat glands ▪ Eccrine glands ▫ Forms over most of body ▫ Buds arise from germinative layer ▫ Buds grow into dermis ▫ Terminal part coils, forms secretory part of glands ▪ Apocrine glands ▫ Develop during puberty over hairy parts of the body ▫ Arise from epidermal buds that produce OSMOSIS.ORG 247

hair follicles Mammary glands ▪ Modified sweat glands ▪ Arise as bilateral bands of thickened epidermis (AKA mammary lines/mammary ridges) ▪ Week 7: these lines extend from from base of forelimb to base of hindlimb ▫ Most of the line disappears, except in thoracic region ▪ Mammary lines penetrate mesenchyme, give rise to 16–24 sprouts that form small buds ▪ By end of intrauterine life, sprouts are canalized, form lactiferous ducts ▪ Lactiferous ducts initially open into small epithelial pit ▫ Shortly after birth, proliferate, transform into nipple ▪ At puberty, lactiferous ducts stimulated by estrogen, progesterone to form alveoli, secretory cells 248 OSMOSIS.ORG