done 2.pdf

Skeletal muscle embryology CU: Animal Body Function IX Alexandre Trindade, PhD Skeletal muscle is also known as voluntary, striated, or segmental muscle. The last term refers to the origin of most of the skeletal muscles of the vertebrate body from the segmented paraxial mesoderm, the somites. Det...

Skeletal muscle embryology CU: Animal Body Function IX Alexandre Trindade, PhD Skeletal muscle is also known as voluntary, striated, or segmental muscle. The last term refers to the origin of most of the skeletal muscles of the vertebrate body from the segmented paraxial mesoderm, the somites. Determination and differentiation of skeletal muscle cells The mesoderm is divided into: - Paraxial mesoderm - Intermediate mesoderm - Lateral plate mesoderm The notochord and the ventral wall of the neural tube induces paraxial mesoderm to form: somites somitomeres Mesoderm divides into three parts: paraxial, intermediate, and lateral plate mesoderm. Paraxial Mesoderm: Forms segmented spiral clusters called somitomeres. Somitomeres have a whorl-like pattern and are the precursors to somites. Somitogenesis: Somitomeres differentiate into somites with clear boundaries. Somites further differentiate into dermatome, myotome, and sclerotome, forming essential structures like the skin, skeletal muscles, and vertebrae. Somitomeres: are partially segmented spirals of mesenchymal cells derived from cranial paraxial mesoderm. Muscles of the head are derived from seven somitomeres. Somites are blocks of paraxial mesoderm that are located on either side of the neural tube in the developing vertebrate embryo. Somites are literally the building blocks of the vertebrate body plan; they are essential for segmentation, bone and musculature development, as well as creating a template for the nervous system. Somites form by rearrangement of mesenchymal cells into epithelial-lined balls (happens by mesenchymal-to-epithelial transition – MET). While the cells at the periphery of a somite have the appearance of epithelial cells, those that are centrally located have a mesenchymal appearance and are called the somitocoel. Somitocomere-somite somite-MET: dorsal: epitheial-dermatome lateral: epithelial: myotome medial and ventra: EMT: mesenchymal: sclerotome all periphery in center: stay mesenchymal form: somitocoel The epithelial‐like cells of the medial and ventral walls of each somite differentiate into mesenchymal cells by epithelial-to- mesenchymal transition - EMT. This forms the sclerotomes. 1: Neural groove; 2: Somite; 3: Notochord; 4: Sclerotome; 5: Dermamyotome; 6: Neural tube; 7: Dorsal aorta; 8: Dermatome; 9: Myotome. The sclerotomes and the cells from these regions give rise to connective tissue, including cartilage and bone. Forms most of the axial skeleton (vertebrae, ribs and base of skull). The sclerotomes and the cells from these regions give rise to connective tissue, including cartilage and bone. Forms most of the axial skeleton (vertebrae, ribs and base of skull). Each sclerotome splits into a rostral and a caudal segment. As the spinal neurons grow outward to innervate the muscles from the myotome, the rostral segment of each sclerotome combines with the caudal segment of the next anterior sclerotome to form a vertebral rudiment, in a process known as resegmentation.  Under the influence of secreted products produced by the dorsal neural tube and the surface ectoderm, the dorsal half of the epithelial somite becomes transformed into the dermomyotome. dorsal neural tube and surface ectoderm secrete signaling molecules cells in the dorsal half of somite receive it and these cells tranform themself into dermomyotome to form dermis and skeletal muscle tissue Dorsal and lateral part need these signaling molecules to differentiate into dermatome and myotome 1: Neural groove; 2: Somite; 3: Notochord; 4: Sclerotome; 5: Dermamyotome; 6: Neural tube; 7: Dorsal aorta; 8: Dermatome; 9: Myotome. Cells of the central region of the somite give rise to the dermatome which contributes to the formation of the dermis of the skin (dermoblasts), brown fat and myoblasts. Somite epithelial cells from the dorso‐medial (DML) and ventro‐lateral (VLL) lips (or edges) undergoes EMT to form myogenic cells that migrate ventral to the dermatome, thereby forming the myotome. The mesenchymal cells in the somitocoel contribute to the dermomyotome, providing additional cells that will differentiate into specific tissues. Committed myogenic cells pass through several additional mitotic divisions before completing a terminal mitotic division and becoming postmitotic myoblasts. Some myogenic cells remain undifferentiated. These undifferentiated cells become skeletal muscle stem cells called satellite cells, and they are responsible for postnatal muscle growth and muscle repair. 1, neural tube; 2, notochord; 3, aorta; 4, surface ectoderm; 5, Wolffian duct; 6, dorsal somite half; 7, ventral somite half; 8, somitocoel cells/arthrotome; 9, central sclerotome; 9a, anterior half of central sclerotome; 9b, posterior half of central sclerotome; 10, ventral sclerotome; 11, lateral sclerotome; 12, dorsal sclerotome; 13, meningeal precursors; 14, axial tendon precursors/syndetome; 15, dermomyotome; 16, epaxial myotome; 17, hypaxial myotome; 18, von Ebner’s fissure; 19, spinal nerve. Differentiation of muscle fibers The mononucleated myoblasts, elongate and undergo repeated mitotic divisions, subsequently fusing with each other to form syncytia. Each syncytium becomes a multinucleated myotube with continuous cytoplasm, and the numerous nuclei within it are centrally located. The multinucleated myotubes of skeletal muscle become muscle fibers as myofilaments of actin and myosin are laid down within the cytoplasm, which are precisely arranged, forming contractile units, the sarcomeres. As the number of myofibrils increases, the nuclei of the myotubes, which had been arranged in regular central chains, migrate to the periphery of the myotube and become located directly beneath the sarcolemma. The nuclei of the muscle fibers themselves, once in place, do not divide mitotically or amitotically; consequently, new myoblasts have to incorporated into the syncytia for fibers to grow in length.  Beyond the fetal growth phase, muscle fiber growth is accomplished by means of a population of myogenic cells, called satellite cells, which take up positions between the muscle fiber and the basal lamina in which each muscle fiber encases itself. myotome have progenitor cells-myoblast-divide-fuse together to form myotubes inside myotube: protein (actin/myosin): myofillaments Myofilament arranged: sarcomeres become mature muscle fibers the satellite cells remain inactive until they are needed for muscle repair or growth Histogenesis of muscle When the earliest myoblasts fuse into myotubes, they give rise to primary myotubes, which form the initial basis for an embryonic muscle. The differentiation of primary myotubes occurs before motor nerve axons have entered the newly forming muscle. Subsequently, smaller secondary myotubes arising from late myoblasts form alongside the primary myotubes. By the time secondary myotubes form, early motor axons are present in the muscles. Innervation of muscle Muscle as a tissue consists not only of muscle fibers, but also of connective tissue, blood vessels, and nerves. While muscles first form, the myoblasts are intermingled with future connective tissue mesenchyme. Capillary sprouts grow into the forming muscle for nourishment, and motor nerve fibers enter shortly after the first myoblasts begin forming myotubes. spinal nerve come from spinal cord and give: somite diff give sclerotome, dermatome, myotome dorsal primary branch: go to back muscle ventral primary branch: fo to muscle in front sides and llimbs myotome part: epimere: part of mytome give back muscles and get nerve supply from dorsal.. hypomere: part mytome become mucles front, side, limbs supply by ventral.. Spinal nerves develop in association with each developing somite. Each spinal nerve gives off a dorsal primary branch to an epimere and a ventral primary branch to a hypomere. Each adult muscle is innervated by more than one spinal nerve because most skeletal muscles of the body derive from fusion of more than one myotome. the dorsal part of the somite differentiate into myotome, some of them give at the end sarcomere, some of them do not differentiate and give satellite cells that help later, and some of them can be in a myotome part and in a hypomere part each of them innervate by a nerve thta come from dorsal or ventral primary branch The contribution of the somitomeres and somites to the formation of muscles and their distinct innervation is unchanged throughout growth and development. Thus although many muscles migrate in location, their nerve supply is maintained and hence their origin can always be identified. As epimeres and hypomeres are somite‐derived, the muscle groupings formed are initially arranged segmentally along a cranial–caudal axis. The hypomeric muscle bundles proliferate and extend ventrally, forming its primordial musculature, which initially remains segmented. Subsequently, with the exception of those in the thoracic region, the hypomeres fuse. In the adult, myotome is the group of muscles on one side of the body that are innervated by one spinal nerve root. Together with dermatomes, they represent some of the segmentation of the vertebrate body. Morphogenesis of head and neck muscles The skeletal musculature of the head originates from myoblasts which arise from somitomeres and migrate to the pharyngeal arches. Somitic paraxial mesoderm contributes to tongue muscles and pharyngeal constrictor muscles. Neck muscles derive from pharyngeal arch mesoderm (cardiopharyngeal mesoderm) and are so innervated by cranial nerve XI. atp, acromiotrapezius; ccl, cucullaris; epm, epaxial neck musculature; hpm, hypaxial neck musculature; PA1-2, pharyngeal arches 1–2; stm, sternocleidomastoid (brachiocephalic muscle); stp, spinotrapezius;. Mucles of the head and neck BRANCHIOMERIC (i.e. in branchial arches – aka pharyngeal arches) Arise from unsegmented paraxial mesoderm (i.e. somitomeres) that migrates into arches 1-3: - Arch 1: muscles of mastication, tensor tympani, tensor veli palantini, anterior belly of digastric (CN-V) - Arch 2: muscles of facial expression, stapedius, stylohyoid, posterior belly of digastric (CN-VII) - Arch 3: stylopharyngeus (CN-IX) Arise from segmented (somitic) paraxial mesoderm that migrates into arches 4 and 6: - Arch 4: pharyngeal constrictors, levator veli palatini (superior laryngeal branch of CN-X) - Arch 6: intrinsic laryngeal muscles (recurrent laryngeal branch of CN-X) Arise from occipital posterior cardiopharyngeal mesoderm adjacent to somites 1-3 - Trapezius, brachiocephalic (partly), omotransversarius [dorsal branch], sternocephalicus and cleidocephalicus mm [ventral]. (CN-XI) SOMATIC (i.e. NOT in pharyngeal arches) Arise from unsegmented paraxial mesoderm (i.e. somitomeres) that does NOT migrate into arches: - Extraocular muscles (CN-III, -IV, -VI) Arise from somitic paraxial mesoderm that migrates into the tongue after its formation: - Intrinsic and extrinsic muscles of the tongue (CN-XII) Morphogenesis of trunk and limbs muscles Some myoblasts come from the VLL, cross the lateral somitic frontier (green line), and enter the lateral plate mesoderm forming the ventral hypomeres (hypaxial muscles – ventrolateral muscles – ventral to the transverse process). Myoblasts from DML and the VLL myoblasts that don’t migrate, remain in the paraxial mesoderm and form the epimeres (epaxial muscles – erector spinae muscles – dorsal to the transverse process). In the limb regions, myogenic cells immigrate from the DML to form extensor muscles; and VLL to form flexor muscles. At the level of the fore- and hindlimbs, cells delaminate from the hypaxial dermomyotome and migrate into the early limb. Formation of intrinsic muscles of the limb is controlled by local cues from the limb mesenchyme. After the premuscle masses for extrinsic muscles of the limb have formed, cells from their proximal portions move back to the trunk. This process has been termed the “In-Out mechanism”. Ribs develop in the undifferentiated mesenchyme between the segmentally-arranged intercostal muscles. The hypomeres in the thoracic region, while retaining their segmented arrangement, give rise to three muscle layers: external and internal intercostal muscles transverse thoracic muscles In the abdominal region, individual hypomeres fuse forming a continuous muscular sheet, which subsequently gives rise to three muscle layers: external and internal oblique abdominal muscles the transverse abdominal muscles The ventral portions of the proliferating hypomeres which separate from the main muscle bands fuse, forming the primordium of the rectus abdominis muscle. Myoblasts from the hypomeres in the lumbo‐sacral region give rise to: sublumbar muscles psoas major and psoas minor muscles quadratus lumborum muscle In the sacro‐caudal region, myoblasts give rise to the muscles of the pelvic diaphragm, comprised of coccygeus muscle levator ani muscle  Embryological origins of tendons Some cells of myotome-lateral plate mesoderm-hypoxial muscles-form limbs cells from hypoxial dermomyotome move into early limb formation control by signals from the limb mesenchyme after initial muscle group for the limbs form some cells move back to the trunk: in-out mechanism Hypomere Cells: Limb Formation: In-Out Mechanism: Some hypomere cells migrate into the early limb to form limb muscles and some return to the trunk. Thoracic Region (Chest): Hypomere cells form the following muscles: External Intercostal Muscles Internal Intercostal Muscles Transverse Thoracic Muscles Abdominal Region: Hypomere cells fuse to form a continuous muscle sheet, which then splits into three layers: External Oblique Muscles Internal Oblique Muscles Transverse Abdominal Muscles Lower Back and Sacral Area: Hypomere cells form the following muscles: Sublumbar Muscles Psoas Major Muscle Psoas Minor Muscle Quadratus Lumborum Muscle Sacro-Caudal Region: Hypomere cells form the following muscles of the pelvic floor: Coccygeus Muscle Levator Ani Muscle Undifferentiated mesoderm-derived cells or mesenchymal stem cells are able to differentiate into different types of connective tissues including, bone, cartilage, tendon, and irregular connective tissue. Tendons can be divided into head, axial, and limb tendons. Head tendons originate from neural crest cells (orange). Axial tendons originate from somites (purple). Limb tendons originate from limb lateral plate mesoderm (green). Whatever the tendon group, tendons share the same embryological origins with skeletal tissues such as cartilage and bone, and have origins distinct from those of skeletal muscles. In vertebrae, tendons originate from the syndetome, while axial muscles originate from the dermatomyotome. In the head, neural crest cells give rise to facial skeleton and tendons, while skeletal muscles originate from head mesoderm. In limbs, both skeleton and tendons originate from limb lateral plate, while skeletal muscles derive from somites.  resumé rapide: Thank you! Paraxial mesoderm-somitocore-somite-MET Periphery region: dorsal: dermatome: dermis skin and myotome: muscle cells lateral: myotome ventral and medial: EMT-sclerotome: ribs, vertebrae center: stay mesenchymal In mytome: epimere part: muscles of back innervate by dorsal primary branch of spinal nerve hypomere: muscles of front, side, limbs innervate by ventral primary branch In myotome: some do not differentiate: satellite cells: help later In myotome: some differentiate: myoblast-myotube-myofibril-sarcomere In myotome: primary myotube: earliest myoblast: form before motor nerve axons enter muscle seocdary myotubes: dvlp when motor nerve are present From ventral/lateral lip: myoblast cross lateral somitic frontier and enter lateral plate mesoderm-hypoxial muscles Dorsal medial lip: no migration, stay in paraxial mesoderm-epaxial muscles