Skeletal Muscle Embryology

Skeletal Muscle Embryology

Glossary Definitions

• Dermatome: Region of skin innervated by a single spinal nerve, and cells of the central somite region contributing to the dermis.
• Dermomyotome: The somite's dorsal portion post-sclerotome separation gives rise to the dermatome and myotome.
• Epimere: The myotome's dorsal part forms epaxial muscles like the erector spinae.
• Epithelial-to-Mesenchymal Transition (EMT): Epithelial cells lose polarity/adhesion, gaining migratory/invasive traits to become mesenchymal stem cells.
• Hypomere: The myotome's ventral portion forms hypaxial muscles like lateral/ventral trunk and limb muscles.
• Mesenchymal-to-Epithelial Transition (MET): Mesenchymal stem cells turn into epithelial cells.
• Mesoderm: The middle germ layer forms muscles, bones, blood vessels, and other tissues.
• Myoblast: The mononucleated precursor of muscle fibers.
• Myotome: The somite portion that forms muscle tissue, or a muscle group innervated by a single spinal nerve root.
• Myotube: A multinucleated immature muscle fiber from fused myoblasts.
• Notochord: A mesoderm-derived rod that supports the developing embryo and induces the neural tube's formation.
• Paraxial Mesoderm: The mesoderm portion closest to the notochord; gives rise to somites and somitomeres.
• Sarcolemma: The muscle fiber's cell membrane.
• Sarcomere: The actin/myosin filament-composed basic contractile unit of a muscle fiber.
• Satellite Cells: Muscle stem cells between the muscle fiber and basal lamina; responsible for muscle growth/repair.
• Sclerotome: The somite's ventromedial portion; forms cartilage/bone of the axial skeleton.
• Somite: Segmented mesoderm blocks along the neural tube that form vertebrae, ribs, muscles, and dermis.
• Somitocoel: The central cavity of a somite.
• Somitomere: Partially segmented mesenchyme spirals from cranial paraxial mesoderm.
• Syndetome: The sclerotome region that gives rise to axial tendons.

Skeletal Muscle

• Skeletal muscle is also known as voluntary, striated, or segmental muscle.
• Segmented paraxial mesoderm is the origin of most vertebrate skeletal muscles.

Determination and Differentiation of Skeletal Muscle Cells

• Mesoderm divides into paraxial, intermediate, and lateral plate mesoderm.
• Paraxial mesoderm forms somites and somitomeres due to the notochord and ventral neural tube.
• Somitomeres are partially segmented mesenchymal cell spirals from cranial paraxial mesoderm.
• Seven somitomeres derive the muscles of the head.
• Blocks of paraxial mesoderm called somites are located on both sides of the neural tube in a developing vertebrate embryo.
• Somites are required for segmentation, bone and muscle growth, and also a template for the nervous system.
• Somites are created via mesenchymal-to-epithelial transition (MET).
• Somitocoel: cells at the periphery of a somite appear epithelial, those centrally located have a mesenchymal appearance.
• Each somite's medial/ventral epithelial-like cells differentiate into mesenchymal cells via EMT which forms the sclerotomes.
• Sclerotomes form connective tissue, cartilage, and bone.
• Sclerotomes form most of the axial skeleton, including vertebrae, ribs, and the skull base.
• The dorsal epithelial somite becomes a dermomyotome due to the dorsal neural tube and surface ectoderm.

Dermomyotome

• Cells of the central dermomyotome form the dermatome, which helps to form the dermis and (dermoblasts), brown fat and myoblasts of the skin.
• Dermomyotome cells from the dorsomedial (DML) and ventrolateral (VLL) lips undergo EMT to create muscle progenitor cells (MPCs).
• MPCs migrate ventrally into dermatome, forming the myotome.
• Committed muscle progenitor cells undergo mitotic divisions and then become postmitotic myoblasts.
• Some muscle progenitor cells stay undifferentiated and become skeletal muscle stem cells (satellite cells).
• Satellite cells are responsible for postnatal muscle growth and repair.

Differentiation of Muscle Fibers

• Mononucleated myoblasts elongate undergo repeated mitotic divisions, fusing to form syncytia.
• Each syncytium becomes a multinucleated myotube, with numerous centrally located nuclei and continuous cytoplasm.
• Myotubes become muscle fibers with actin and myosin myofilaments arranged precisely to form contractile sarcomeres.
• Myotube nuclei migrate to the periphery beneath the sarcolemma as myofibrils increase.
• Fetal growth phase requires satellite cells to situate between muscle fiber and basal lamina for muscle fiber growth.
• Myoblasts fuse into myotubes to form primary myotubes for embryonic muscle while secondary myotubes develop alongside from other myoblasts.

Morphogenesis of Head and Neck Muscles

• Skeletal muscles of the head originate from somitomere-derived myoblasts that move to the pharyngeal arches.
• Somitic paraxial mesoderm leads to the tongue and pharyngeal constrictor muscles
• Neck muscles come from the pharyngeal arch mesoderm (cardiopharyngeal mesoderm) and are innervated by cranial nerve XI.

Muscles of the head and neck are formed in the following ways

• Branchiomeric muscles made from unsegmented paraxial mesoderm migrate into pharyngeal arches 1-3.
• Muscles of facial expression come from arch 2.
• Stylopharyngeus comes from arch 3.
• Arch 4 makes pharyngeal constrictors.
• Intrinsic laryngeal muscles come from arch 6.
• Occipital cardiopharyngeal mesoderm forms trapezius and other muscles.
• Somitic paraxial mesoderm not from the arches forms extraocular muscles or intrinsic/extrinsic tongue muscles.

Morphogenesis of Trunk and Limbs Muscles

• Myoblasts from the dorsomedial lip (DML) and ventrolateral lip (VLL) that do not migrate are located in the paraxial mesoderm and produce the epimeres (epaxial muscles).
• Myoblasts from the VLL cross the lateral somitic frontier to makes the hypomeres, which are ventral or ventrolateral muscles.
• Limbs grow out as limb buds.
• Proximal to distal limb regions develop in order.
• Separate digits from digit necrotic zones.
• Extensor muscles come from DML myogenic cells.
• Flexor muscles come from VLL myogenic cells.

Somite Divisions

• Epimere forms intrinsic back muscles, innervated by the dorsal ramus of spinal nerves.
• Hypomere develops into the body wall and limb musculature which are innervated by the ventral ramus of the spinal nerves.
• Hypomeric muscle bundles increase, forming primordial musculature.
• Hypomeres fuse, except in the thoracic region.
• Lumbo-sacral hypomeres give rise to sublumbar, psoas major and minor, and quadratus lumborum muscles and sacro-caudal ones give rise to coccygeus and levator ani muscles.

Innervation of muscle

• Initial muscle groupings are arranged segmentally.
• Myotome: refers to muscles innervated by a single spinal nerve root.
• Muscles have connective tissue, blood vessels, and nerves.
• Myoblasts intermingle connective tissues and capillary sprouts for muscle nourishment.
• Muscle tissues receives motor nerve fibers shortly after.
• Spinal nerves form with each somite, giving off dorsal branches to epimere and ventral branches to hypomere.
• Adult muscles are innervated by more than one spinal nerve because skeletal muscles derive from multiple myotomes.
• Location does not change the contribution of the somitomeres or somites to the formation of muscles and their innervation and is maintained throughout development.

Embryological origins of tendons

• Mesoderm-derived cells able to differentiate into connective tissues.
• Head tendons originate from neural crest cells.
• Axial tendons originate from somites.
• Limb tendons originate from the lateral plate mesoderm.
• Tendons share the same embryological origins with the skeletal tissues.
• Tendons originate from the syndetome while axial muscles originate from the dermatomyotome.
• Head skeleton/tendons form from neural crest cells.
• Head muscles form from head mesoderm.
• Limbs originate from limb lateral plate, while limb skeletal muscles derive from somites.