Muscular System Introduction Develops from mesoderm, except for: iris muscles: develop from neuroectoderm esophagus muscles believed to develop by transdifferentiation from smooth muscle Day 17 MyoD, a member of the family of myogenic regulatory factors, activates transcription of muscle-specific genes and is considered an important regulatory gene for the induction of myogenic differentiation The induction of myogenesis in mesenchymal cells by MyoD is dependent on their degree of mesenchymal cell differentiation. Much of mesenchyme in the head is derived from the neural crest, particularly tissues derived from the pharyngeal arches original mesenchyme in these arches gives rise to face and neck musculature

Paraxial Mesoderm Thick plate of mesoderm on each side of midline Becomes organized into segments known as somitomeres: form in a craniocaudal sequence Somitomeres 1–7 do not form somites contribute mesoderm to head and neck region (pharyngeal arches) Remaining somitomeres further condense to form 42–44 pairs of somites: Somites closest to caudal end eventually disappear: giving rise to a final count of about 35 pairs of somites Day 19

Somites Differentiate into three components: Sclerotome: Myotome: cartilage and bone component Myotome: muscle component Dermatome: dermis of skin component Stages in development of a somite. Mesoderm cells are arranged around a small cavity. Cells of the ventral and medial walls of the somite lose their epithelial arrangement and migrate in the direction of the notochord. These cells collectively constitute the sclerotome. Cells at the dorsolateral portion of the somite migrate as precursors to limb and body wall musculature. Dorsomedial cells migrate beneath the remaining dorsal epithelium of the somite to form the myotome. Cells forming the myotome continue to extend beneath the dorsal epithelium. After ventral extension of the myotome, dermatome cells lose their epithelial configuration and spread out under the overlying ectoderm to form dermis.

Myotomes Part of a somite that divides into: 1 Part of a somite that divides into: 1 dorsal epaxial division 2 ventral hypaxial division Developing spinal nerves divide and send a branch to each myotome division: dorsal primary ramus supplies: epaxial division ventral primary ramus supplies: hypaxial division 2 Erector spinae and other back muscles innervated by epimer/dorsal, everything else innervated by ventral. A, Sketch of an embryo (approximately 41 days) showing the myotomes and developing muscular system. B, Transverse section of the embryo illustrating the epaxial and hypaxial derivatives of a myotome. C, Similar section of a 7-week embryo showing the muscle layers formed from the myotomes. Gene targeting studies in the mouse embryo suggest that MyoD and Myf-5 genes are essential for the development of the hypaxial and epaxial muscles, respectively Both genes are involved in the development of the abdominal and intercostal muscles Some muscles (e.g., intercostal muscles) remain segmentally arranged like the somites most myoblasts migrate away from the myotome and form nonsegmented muscles

Development of Skeletal Muscle First indication of myogenesis (muscle formation) is: elongation of nuclei and cell bodies of mesenchymal cells: differentiate into primordial muscle cells called myoblasts Myoblasts fuse to form: elongated, multinucleated, cylindrical structures called myotubes During or after fusion of myoblasts: myofilaments develop in cytoplasm of myotubes organize into myofibrils Because muscle cells are long and narrow: they are usually called muscle fibers Muscle fibers are postmitotic further growth is accomplished by satellite cells

Limb Musculature Derived from myotomes in: upper limb bud region lower limb bud region This mesoderm migrates into limb bud and forms: posterior condensation anterior condensation Posterior condensation develops into: extensor and supinator musculature of upper limb extensor and abductor musculature of lower limb Anterior condensation develops into: flexor and pronator musculature of upper limb flexor and adductor musculature of lower limb

Development Of Smooth Muscle Smooth muscle fibers differentiate from: splanchnic mesenchyme surrounding endoderm of primordial gut and its derivatives Somatic mesoderm provides: smooth muscle in walls of many blood and lymphatic vessels Muscles of the iris (sphincter and dilator pupillae) and myoepithelial cells in mammary and sweat glands are derived from: mesenchymal cells that originate from ectoderm ~20 Days A, Sketch of an embryo (approximately 41 days) showing the myotomes and developing muscular system. B, Transverse section of the embryo illustrating the epaxial and hypaxial derivatives of a myotome. C, Similar section of a 7-week embryo showing the muscle layers formed from the myotomes. ~21 Days

Development of Cardiac Muscle (slide 1 of 2) Develops from the lateral splanchnic mesoderm gives rise to mesenchyme surrounding developing heart tube Cardiac myoblasts differentiate to form primordial myocardium Heart muscle is recognizable in fourth week Cardiac muscle fibers arise by differentiation and growth of single cells unlike striated skeletal muscle fibers that develop by fusion of cells 17 days 18 days Transverse sections through embryos at different stages of development, showing formation of a single heart tube from paired primordia. Early presomite embryo (17 days). Late presomite embryo (18 days). Eight-somite stage (22 days). Fusion occurs only in the caudal region of the horseshoe-shaped tube (see Fig. 12.4). The outflow tract and most of the ventricular region form by expansion and growth of the crescent portion of the horseshoe. 22 days

Duchenne Muscular Dystrophy (DMD) X-linked recessive disorder caused by: mutation in the gene for dystrophin on the short arm of chromosome X (Xp21) means that males who inherit only one defective copy of the DMD gene from the mother have the disease Dystrophin anchors cytoskeleton (actin) of skeletal muscle cells to extracellular matrix through a transmembrane protein (α-dystroglycan and β-dystroglycan) and stabilizes the cell membrane mutation of the DMD gene destroys the ability of dystrophin to anchor actin to the extracellular matrix Characteristic dysfunction in DMD is: progressive muscle weakness and wasting Death occurs as a result of: cardiac or respiratory failure, usually in late teens or 20’s DMD (no dystrophin) and Becker muscular dystrophy (faulty dystrophin). DMD (no dystrophin) and Becker muscular dystrophy (faulty dystrophin). Duchenne muscular dystrophy (DMD). Immunofluorescent staining for dystrophin shows intense staining at the periphery of skeletal muscle cells in normal individuals and complete absence of staining in the DMD patient.

Lecture Summary Skeletal muscle is derived from? Myotome regions of somites Cardiac muscle and most smooth muscle are derived from? Splanchnic mesoderm

Development of Bone and Cartilage As notochord and neural tube form, intraembryonic mesoderm (lateral to these structures) thickens to form: two longitudinal columns of paraxial mesoderm Toward end of third week, paraxial mesoderm: becomes segmented into blocks of mesoderm called somites - sclerotome Externally, appear as beadlike elevations along dorsolateral surface of embryo Dorsal view ~18 days Transverse Section ~18 days Illustrations of the formation and early differentiation of somites. A, Dorsal view of an embryo of approximately 18 days. B, Transverse section of the embryo shown in A illustrating the paraxial mesoderm from which the somites are derived. C, Transverse section of an embryo of approximately 22 days showing the appearance of the early somites. Note that the neural folds are about to fuse to form the neural tube. Instructive signals from the primitive streak region induce notochordal precursor cells to form the notochord, a cellular rodlike structure The notochord: Defines primordial longitudinal axis of embryo and gives it some rigidity Provides signals that are necessary for development of axial musculoskeletal structures and the central nervous system Contributes to the intervertebral discs Transverse Section ~22 days

Bone Formation All bones are derived from either direct or indirect conversion of preexisting connective tissue called mesenchyme (embryonic connective tissue) into bone This process is called ossification During development, two types of ossification occur: Intramembranous ossification Endochondral ossification

Endochondral Ossification (slide 2) Ossification of limb bones begins at end of embryonic period makes demands on maternal supply of calcium and phosphorus Pregnant women are advised to maintain an adequate intake of these elements to preserve healthy bones and teeth At birth, diaphyses are largely ossified, but: most of epiphyses are still cartilaginous Secondary ossification centers appear: in the epiphyses of most bones during first few years after birth In most bones, epiphyses have fused with diaphysis by: 20 years of age Epiphysial cartilage cells hypertrophy, and there is invasion by vascular connective tissue Ossification spreads radially, and only the articular cartilage and a transverse plate of cartilage, the epiphysial cartilage plate, remain cartilaginous Upon completion of growth, this plate is replaced by spongy bone epiphyses and diaphysis are united, and no further elongation of the bone occurs

Rickets Disease that occurs in children who have a vitamin D deficiency Vitamin D is required for: calcium absorption by the intestine Resulting calcium deficiency causes: disturbances in ossification of the epiphysial cartilage plates (i.e., they are not adequately mineralized) Limbs are shortened and deformed, with severe bowing of the limb bones Osteomalacia in adults

Cartilage Formation Cartilage develops from mesenchyme : first appears during fifth week Mesenchymal cells differentiate into chondroblasts: secrete collagenous fibrils and ground substance (extracellular matrix) Form isogenous groups Histogenesis of hyaline cartilage. A: The mesenchyme is the precursor tissue of all types of cartilage. B: Mitotic proliferation of mesenchymal cells gives rise to a highly cellular tissue. C: Chondroblasts are separated from one another by the formation of a great amount of matrix. D: Multiplication of cartilage cells gives rise to isogenous groups, each surrounded by a condensation of territorial (capsular) matrix. In areas where cartilage is to develop, mesenchyme condenses to form chondrification centers

Development of the Axial Skeleton Composed of: cranium (skull) vertebral column ribs sternum During fourth week, sclerotome cells surround: neural tube (primordium of spinal cord) notochord (structure about which primordia of vertebrae develop) This positional change of sclerotomal cells is effected by differential growth of surrounding structures and not by active migration of sclerotomal cells. The Pax-1 gene, which is expressed in all prospective sclerotomal cells of epithelial somites in chick and mouse embryos, seems to play an essential role in the development of the vertebral column. Transverse section through 4-week embryo

Development of the Vertebral Column During precartilaginous or mesenchymal stage, mesenchymal cells from sclerotomes are found in three main areas: around the notochord surrounding the neural tube in the body wall In a frontal section of a 4-week embryo: sclerotomes appear as paired condensations of mesenchymal cells around notochord Frontal section Paired condensation of schlerotome. A, Transverse section through a 4-week embryo. The arrows indicate the dorsal growth of the neural tube and the simultaneous dorsolateral movement of the somite remnant, leaving behind a trail of sclerotomal cells. B, Diagrammatic frontal section of this embryo showing that the condensation of sclerotomal cells around the notochord consists of a cranial area of loosely packed cells and a caudal area of densely packed cells. Transverse section through 4-week embryo

Each Condensation of Sclerotomal Cells Consists of: loosely arranged cells, cranially densely packed cells, caudally Some densely packed cells move cranially, opposite the center of the myotome: form intervertebral (IV) disc C, Transverse section through a 5-week embryo showing the condensation of sclerotomal cells around the notochord and neural tube, which forms a mesenchymal vertebra. D, Diagrammatic frontal section illustrating that the vertebral body forms from the cranial and caudal halves of two successive sclerotomal masses. The intersegmental arteries now cross the bodies of the vertebrae, and the spinal nerves lie between the vertebrae. The notochord is degenerating except in the region of the intervertebral disc, where it forms the nucleus pulposus. Transverse section through 5-week embryo Frontal section

Development of the Vertebral Body Remaining densely packed sclerotome cells: fuse with loosely arranged cells of the immediately caudal sclerotome to form: mesenchymal centrum primordium of vertebral body each centrum develops from two adjacent sclerotomes Nerves lie close to intervertebral discs and intersegmental arteries lie on each side of vertebral bodies: In the thorax, intersegmental arteries become intercostal arteries Nerves can exit on top of body

Cartilaginous Stage of Vertebral Development During sixth week, chondrification centers (site of earliest cartilage formation) appear in each mesenchymal vertebra Two chondrification centers in each centrum: fuse at end of embryonic period to form cartilaginous centrum Concomitantly, chondrification centers in the neural arches: fuse with each other and the centrum Spinous and transverse processes develop from: extensions of chondrification centers in the neural arch Chondrification spreads until: cartilaginous vertebral column is formed Stages of vertebral development. A, Mesenchymal vertebra at 5 weeks. B, Chondrification centers in a mesenchymal vertebra at 6 weeks. The neural arch is the primordium of the vertebral arch. C, Primary ossification centers in a cartilaginous vertebra at 7 weeks. D, Thoracic vertebra at birth consisting of three bony parts. Note the cartilage between the halves of the vertebral arch and between the arch and the centrum (neurocentral joint). E and F, Two views of a typical thoracic vertebra at puberty showing the location of the secondary centers of ossification. Mesenchymal vertebra at 5 weeks Mesenchymal vertebra at 6 weeks

Bony Stage of Vertebral Development Ossification of typical vertebrae: begins during embryonic period usually ends by 25th year There are two primary ossification centers for the centrum: ventral and dorsal fuse to form one ossification center Three primary ossification centers are present by end of embryonic period – week 8: one in centrum one in each half of neural arch Stages of vertebral development. A, Mesenchymal vertebra at 5 weeks. B, Chondrification centers in a mesenchymal vertebra at 6 weeks. The neural arch is the primordium of the vertebral arch. C, Primary ossification centers in a cartilaginous vertebra at 7 weeks. D, Thoracic vertebra at birth consisting of three bony parts. Note the cartilage between the halves of the vertebral arch and between the arch and the centrum (neurocentral joint). E and F, Two views of a typical thoracic vertebra at puberty showing the location of the secondary centers of ossification. Primary ossification centers in a cartilaginous vertebra at 7 weeks

Vertebrae Ossification Ossification becomes evident in: neural arches during eighth week At birth, each vertebra consists of: three bony parts connected by cartilage Bony halves of vertebral arch usually fuse: during first 3 to 5 years first unite in lumbar region and progresses cranially Vertebral arch articulates with centrum at: cartilaginous neurocentral joints: permit vertebral arches to grow as spinal cord enlarges These joints disappear when vertebral arch fuses with centrum during third to sixth years Stages of vertebral development. A, Mesenchymal vertebra at 5 weeks. B, Chondrification centers in a mesenchymal vertebra at 6 weeks. The neural arch is the primordium of the vertebral arch. C, Primary ossification centers in a cartilaginous vertebra at 7 weeks. D, Thoracic vertebra at birth consisting of three bony parts. Note the cartilage between the halves of the vertebral arch and between the arch and the centrum (neurocentral joint). E and F, Two views of a typical thoracic vertebra at puberty showing the location of the secondary centers of ossification.

Spina Bifida Failure of the halves of embryonic neural vertebral arch to fuse Occurs more frequently in girls than boys Most cases of spina bifida (80%) are "open" and covered by a thin membrane Spina bifida occulta Spina bifida with meningocele Test question Diagrammatic sketches illustrating various types of spina bifida and the commonly associated anomalies of the vertebral arch, spinal cord, and meninges: A, Spina bifida occulta. Observe the unfused vertebral arch B, Spina bifida with meningocele C, Spina bifida with meningomyelocele D, Spina bifida with myeloschisis The types illustrated in B to D are referred to collectively as spina bifida cystica because of the cystlike sac associated with them Spina bifida with meningomyelocele Spina bifida with myeloschisis Types illustrated in B to D are referred to collectively as spina bifida cystica because of the cystlike sac associated with them

Hemivertebra In normal circumstances: Hemivertebra results from: developing vertebral bodies have: two chondrification centers that unite Hemivertebra results from: failure of one chondrification centers to appear, thus failure of half of vertebra to form: produce scoliosis: (lateral curvature) of vertebral column There are other causes of scoliosis (e.g., myopathic scoliosis, resulting from spinal muscle weakness) Important Vertebral and rib abnormalities. A, Cervical and forked ribs. Observe that the left cervical rib has a fibrous band that passes posterior to the subclavian vessels and attaches to the manubrium of the sternum. B, Anterior view of the vertebral column showing a hemivertebra. The right half of the third thoracic vertebra is absent. Note the associated lateral curvature (scoliosis) of the vertebral column. C, Radiograph of a child with the kyphoscoliotic deformity of the lumbar region of the vertebral column showing multiple anomalies of the vertebrae and ribs. Note the fused ribs (arrow).

Development of the Appendicular Skeleton Consists of: pectoral and pelvic girdles limb bones Mesenchymal bones form during fifth week as: condensations of mesenchyme in the limb buds Somatic lateral mesoderm!!!! A, An embryo at approximately 28 days showing the early appearance of the limb buds. B, Longitudinal section through an upper limb bud showing the apical ectodermal ridge, which has an inductive influence on the mesenchyme in the limb bud. This ridge promotes growth of the mesenchyme and appears to give it the ability to form specific cartilaginous elements. C, Similar sketch of an upper limb bud at approximately 33 days showing the mesenchymal primordia of the forearm bones. The digital rays are mesenchymal condensations that undergo chondrification and ossification to form the bones of the hand. D, Upper limb at 6 weeks showing the cartilage models of the bones. E, Later in the sixth week showing the completed cartilaginous models of the bones of the upper limb. Formed from Somatic lateral mesoderm!!!! ~28 days Longitudinal section ~33 days

Appendicular Skeleton: Mesenchyme to Cartilage During sixth week, mesenchymal bone models in the limbs undergo chondrification to form hyaline cartilage bone models Clavicle initially develops by intramembranous ossification, and it later forms growth cartilages at both ends Models of the pectoral girdle and upper limb bones appear: slightly before pelvic girdle and lower limb bones Bone models appear in a proximodistal sequence A, An embryo at approximately 28 days showing the early appearance of the limb buds. B, Longitudinal section through an upper limb bud showing the apical ectodermal ridge, which has an inductive influence on the mesenchyme in the limb bud. This ridge promotes growth of the mesenchyme and appears to give it the ability to form specific cartilaginous elements. C, Similar sketch of an upper limb bud at approximately 33 days showing the mesenchymal primordia of the forearm bones. The digital rays are mesenchymal condensations that undergo chondrification and ossification to form the bones of the hand. D, Upper limb at 6 weeks showing the cartilage models of the bones. E, Later in the sixth week showing the completed cartilaginous models of the bones of the upper limb. 6 weeks Later in sixth week

Summary of Lecture (slide 1 of 2) What is the main component in which the skeletal system develops? Mesenchyme, derived from mesoderm In most bones, such as long bones in the limbs, the condensed mesenchyme undergoes what process to form cartilage bone models? Chondrification When do ossification centers appear in these cartilage bone models? By the end of the embryonic period Later, these bones ossify which named process? Endochondral ossification Flat bones ossify by which named process? Intramembranous ossification The vertebral column develop from mesenchymal cells of what structure? Sclerotomes of somites Each vertebra is formed by? Fusion of caudal half of one pair of sclerotomes with cranial half of subjacent pair of sclerotomes

Summary of Lecture (slide 2 of 2) The appendicular skeleton develops from? Endochondral ossification of the cartilaginous bone models, which form from mesenchyme in the developing limbs What are the three classifications of joints? Fibrous joints, cartilaginous joints, and synovial joints Joints develop from? Interzonal mesenchyme between the primordia of bones In a fibrous joint, the intervening mesenchyme differentiates into? Dense fibrous connective tissue In a cartilaginous joint, the mesenchyme between the bones differentiates into? Cartilage In a synovial joint, what forms within the intervening mesenchyme by breakdown of cells? Synovial cavity In a synovial joint, mesenchyme also gives rise to? Synovial membrane, capsule, and ligaments of the joint

Review of Development (slide 1 of 3) Lateral plate mesoderm migrates into limb bud: condenses along the central axis to eventually form: vasculature and skeletal components of limbs Somites of paraxial mesoderm migrate into limb bud: condense to form: musculature component of limbs Apical ectodermal ridge (AER) is a ridge of thickened ectoderm at the apex of the limb bud AER produces FGF (fibroblast growth factor), which interacts with the underlying mesoderm to promote outgrowth of the limb by stimulating mitosis and preventing terminal differentiation of the underlying mesoderm AER expresses the Wnt7 gene that directs the organization of the limb bud along the dorsal-ventral axis Zone of polarizing activity (ZPA) consists of mesodermal cells located at the base of the limb bud ZPA produces sonic hedgehog (a diffusible protein encoded by a segment polarity gene), which directs the organization of the limb bud along the anterior-posterior polar axis and patterning of the digits Sonic hedgehog activates the gene for BMP (bone morphogenetic protein) and the Hoxd-9, Hoxd-10, Hoxd-11, Hoxd-12, and Hoxd-13 genes Retinoic acid also plays a significant role in limb polarization Digit formation occurs as a result of selected apoptosis (cell death) within the AER, such that five separate regions of AER remain at the tips of the future digits Exact mechanism is poorly understood, although BMP, Msx-l, and retinoic acid receptor may play a role

Early Stages of Limb Development (1 of 4) Limb development begins with: activation of mesenchymal cells in lateral mesoderm Limb buds form deep to: thick band of ectoderm called Apical Ectodermal Ridge (ACR) Toward end of fourth week, limb buds first appear as: elevations of ventrolateral body wall Upper limb buds: visible by day 26 or 27 Lower limb buds: appear 1 or 2 days later Each limb bud consists of: mass of mesenchyme derived from: somatic layer of lateral mesoderm covered by ectoderm A, Lateral view of a human embryo at Carnegie stage 13, approximately 28 days. The upper limb buds appear as swellings on the ventrolateral body wall. The lower limb buds are not as well developed. Limb buds elongate by: proliferation of mesenchyme Upper limb buds appear: disproportionately low on embryo's trunk: because of early development of cranial half of embryo Earliest stages of limb development are alike for the upper and lower limbs Because of their form and function: there are many distinct differences between development of the hand and foot Upper limb buds: develop opposite the caudal cervical segments Lower limb buds: form opposite the lumbar and upper sacral segments

Early Stages of Limb Development (3 of 4) Mesenchymal cells proximal to AER differentiate into: blood vessels cartilage bone models Distal ends of limb buds: flatten into paddle-like hand- and footplates By end of sixth week and during seventh week: mesenchymal tissue in handplates and footplates condense to form: digital rays outline pattern of digits or fingers/toes Illustrations of embryonic development of the limbs (32-56 days) Note that development of the upper limbs precedes that of the lower limbs. Endogenous retinoic acid is: involved in limb development and pattern formation At tip of each digital ray: part of AER induces development of mesenchyme into: mesenchymal primordia of bones (phalanges) in the digits

Early Stages of Limb Development (4 of 4) Intervals between digital rays occupied by: loose mesenchyme that breaks down, forming: notches between digital rays as tissue breakdown progresses: separate digits (fingers and toes) are formed by end of eighth week Programmed cell death (apoptosis) is responsible for: tissue breakdown in the interdigital regions incomplete programmed cell death (apoptosis) leads to: syndactyly (webbing of fingers or toes) Illustrations of the development of the hands and feet between the fourth and eighth weeks. The early stages of limb development are alike, except that development of the hands precedes that of the feet by a day or so. A, At 27 days. B, At 32 days. C, At 41 days. D, At 46 days. E, At 50 days. F, At 52 days. G, At 28 days. H, At 36 days. I, At 46 days. J, At 49 days. K, At 52 days. L, At 56 days. The arrows in D and J indicate the tissue breakdown processes the separate the fingers and toes. Various types of digital anomalies. Polydactyly of the hands (A), and foot (B). This condition results from formation of one or more extra digital rays during the embryonic period. Various forms of syndactyly involving the fingers (C), and toes (D). Cutaneous syndactyly (C) is the most common form of this condition and is probably due to incomplete programmed cell death (apoptosis) in the tissues between the digital rays during embryonic life. D, Syndactyly of the second and third toes.

Innervation of Limbs C5 – T1 brachial plexus, Motor axons arising from spinal cord enter limb buds during fifth week: grow into dorsal and ventral muscle masses Sensory axons enter limb buds after motor axons use them for guidance C5 – T1 brachial plexus, L2 – S3 lumbosacral plexus!!!!! C5 – T1 brachial plexus, L2 – S3 lumbosacral plexus!!!!! Strong relationship exist between: limb growth and rotation to cutaneous segmental nerve supply Neural crest cells are: precursors of Schwann cells: surround motor and sensory nerve fibers in the limbs form neurilemmal and myelin sheaths Preaxial and postaxial borders are: cranial and caudal, respectively Illustrations of the development of the dermatomal patterns of the limbs. The axial lines indicate where there is no sensory overlap. A and D, Ventral aspect of the limb buds early in the fifth week. At this stage, the dermatomal patterns show the primordial segmental arrangement. During fifth week, peripheral nerves grow from: developing limb plexuses (brachial and lumbosacral) into mesenchyme of limb Upper Limb Ventral primary rami (C5-T1) arrive at base of limb bud and join to form upper, middle, and lower trunk. Each tr5unk divides into posterior divisions and anterior divisions Posterior divisions grow into posterior condensation and join to form posterior cord Anterior divisions grow into anterior condensation and join to form medial and lateral cords With further development of limb musculature, posterior cord branches into axillary nerve (C5-6) and radial nerve (C5-T1), innervating all muscles that form from posterior condensation With further development of limb musculature, medial cord and lateral cord branch into musculocutaneous nerve (C5-7), ulnar nerve (C8, T1), and median nerve (C5-T1), innervating all muscles that form from anterior condensation. Lower Limb Ventral primary rami from L2-S3 arrive at base of limb bud and divide into posterior and anterior divisions Posterior divisions grow into posterior condensation Anterior divisions grow into anterior condensation With further development of limb musculature, posterior divisions branch into: superior gluteal nerve (L4-S1), inferior gluteal nerve (L5-S2), femoral nerve (L2-L4), and common peroneal nerve (L4-S2); innervating all muscles that form from posterior condensation. With further development of limb musculature, anterior divisions branch into: tibial nerve (L4-S3), and obturator nerve (L2-L4); innervating all muscles that form from anterior condensation

Cutaneous Innervation of Limbs (1 of 2) Dermatome (segmental innervation) is: area of skin supplied by a single spinal nerve and its spinal ganglion Cutaneous nerve areas (multisegmental innervation) is: area of skin supplied by a peripheral nerve that is formed by multiple spinal cord segments Upper limbs lateral rotation, lower – medial rotation!!!!!!!!! Upper limbs lateral rotation, lower – medial rotation!!!!!!!!! If dorsal root supplying the area is cut: dermatomal patterns indicate that there may be a slight deficit in the area indicated Because there is overlapping of dermatomes: a particular area of skin is not exclusively innervated by a single segmental nerve Spinal nerves are distributed in segmental bands: supply both dorsal and ventral surfaces of limb Axial lines indicate where there is no sensory overlap. A and D, Ventral aspect of limb buds early in fifth week. At this stage, dermatomal patterns show primordial segmental arrangement. B and E, Similar views later in fifth week showing the modified arrangement of dermatomes. C and F, The dermatomal patterns in the adult upper and lower limbs. The primordial dermatomal pattern has disappeared but an orderly sequence of dermatomes can still be recognized. F, Note that most of the original ventral surface of the lower limb lies on the back of the adult limb This results from medial rotation of the lower limb occurs toward end of embryonic period In the upper limb: ventral axial line extends along anterior surface of arm and forearm In the lower limb: ventral axial line extends along medial side of thigh and knee to posteromedial aspect of leg to heel

Summary of Limb Development When and how do limb buds appear in the embryo? Toward the end of the fourth week as slight elevations of the ventrolateral body wall What is the temporal relationship between the development of upper and lower limb bud development? The upper limb buds develop approximately 2 days before the lower limb buds What are the main sources of tissues for limb bud development? Lateral mesoderm, paraxial mesoderm, and ectoderm What does AER exerts an inductive influence on? The limb mesenchyme, promoting growth and development of the limbs In the distal part of limb development, how is apoptosis (programmed cell death) important in limb development? Formation of the notches between the digital rays, giving rise to fingers and toes Limb muscles are derived from? mesenchyme (myogenic precursor cells) originating in the somites What do the muscle-forming cells (myoblasts) form? dorsal and ventral muscle masses or condensations When do nerves grow into the limb buds? After the muscle masses have formed Most blood vessels of the limb buds arise as? Buds from intersegmental arteries Which direction do the upper and lower limbs rotate? Upper limb rotates laterally 90 degrees and the lower limb rotates medially 90 degrees