Embryology: LC8 Muscular System PDF

Lateral somitic frontier ○ a well defined border between each somite and the O...

Lateral somitic frontier ○ a well defined border between each somite and the OUTLINE parietal layer of lateral plate mesoderm ○ separates two mesodermal domains in the embryo: I. MUSCULAR SYSTEM OVERVIEW II. STRIATED SKELETAL MUSCULATURE 1. Primaxial domain III. INNERVATION OF AXIAL SKELETAL MUSCLES - comprises the region around the neural tube IV. SKELETAL MUSCLE AND TENDONS - contains somite-derived cells. V. MOLECULAR REGULATION OF MUSCLE DEVELOPMENT 2. Abaxial domain VI. HEAD MUSCULATURE - consists of the parietal layer of lateral plate VII. LIMB MUSCULATURE mesoderm together with somite cells that VIII. CARDIAC MUSCLES have migrated across the lateral somitic IX. SMOOTH MUSCLE frontier. X. CLINICAL CORRELATIONS I. MUSCULAR SYSTEM OVERVIEW The muscular system develops from the mesodermal germ layer and consists of skeletal, smooth and cardiac muscle Skeletal muscle ○ derived from paraxial mesoderm ○ form somites from the occipital to the sacral regions and somitomeres in the head Smooth muscle ○ differentiates from visceral splanchnic mesoderm surrounding the gut ○ from ectoderm (pupillary, mammary gland, and sweat Table 1. Origins of Muscles from Abaxial and Primaxial Precursors. aThe precise gland muscles) origin of muscles in the pelvic region and lower limb has not been determined, Cardiac muscle but most, if not all, are abaxial in origin. ○ derived from visceral splanchnic mesoderm surrounding the heart tube. II. STRIATED SKELETAL MUSCULATURE Head musculature is derived from seven somitomeres, partially segmented whorls of mesenchymal cells derived from paraxial mesoderm. Musculature of the axial skeleton, body wall, and limbs is derived from somites, which initially form as somitomeres and extend from the occipital region to the tail bud. Somitomeres ○ undergo a process of epithelialization from a "ball" of epithelial cells with a small cavity in the center. Sclerotome ○ the ventral region of each somite then becomes mesenchymal again ○ bone forming cells for the vertebrae and ribs Upper region of the somites become: ○ Dermatome ○ Ventrolateral lip some cells also migrate into the adjacent parietal layer of the lateral plate mesoderm formation of the infrahyoid, abdominal wall Figure 1. Cross-sectional drawings showing the stages of development in a (rectus abdominis, internal and external somite. A) Mesoderm cells become epithelial and are arranged around a small oblique, and transverse abdominus), and limb lumen. B) Cells in the ventral and medial walls of the somite lose their epithelial muscles. characteristics and migrate around the neural tube and notochord, and some ○ Dorsomedial lip move into the parietal layer of lateral plate mesoderm. Collectively, these cells remaining cells in the myotome form muscles constitute the sclerotome. Cells at the DML and VLL regions of the somite form of the back, shoulder girdle and intercostal muscle cell precursors. Cells from both regions migrate ventral to the muscles dermatome to form the dermomyotome. VLL cells also migrate into the parietal Dermomyotome layer of lateral plate mesoderm across the lateral somitic frontier (green line). In ○ forms in cells from these two areas (VLL) and (DLL) combination, somitic cells and lateral plate mesoderm cells constitute the migrate and proliferate to form progenitor muscle cells abaxial mesodermal domain, while the primaxial mesodermal domain only ventral to the dermatome contains somitic cells (paraxial mesoderm). Page 1 of 5 [EMBRYOLOGY] 1.08 EMBRYONIC DEVELOPMENT OF THE MUSCULAR SYSTEM – Dr. Modesto David A. Bolislis, MD Muscle cells that cross this frontier and enter the lateral plate ○ SCLERAXIS - transcription factor that regulates mesoderm comprise the abaxial muscle cell precursors and receive development of tendons. many of their signals for differentiation from lateral plate mesoderm. Those that remain in the paraxial mesoderm and do not cross the frontier comprise the primaxial muscle cell precursors and receive V. MOLECULAR REGULATION OF MUSCLE DEVELOPMENT many of their developmental signals from the neural tube and notochord. Bone morphogenetic protein 4 (BMP4) and probably fibroblast Regardless of their domain, each myotome receives its innervation growth factors from lateral plate mesoderm, together with WNT from the spinal nerves derived from the same segment as the muscle proteins from adjacent ectoderm, signal VLL (ventrolateral lip) cells cells. of the dermomyotome to express the muscle-specific gene MyoD. ○ BMP4 III. INNERVATION OF AXIAL SKELETAL MUSCLES secreted by ectoderm cells induces production of WNT proteins by the dorsal neural tube The new description of muscle development characterized by primaxial and ○ Sonic hedgehog (SHH) proteins abaxial domains differs from the old concept of epimeres (back muscles) secreted by the notochord and floor plate of and hypomeres (limb and body wall muscles), which was based on a the neural tube functional definition of innervation reach the DML (dorsomedial lip) cells of the ○ Epimeric muscles: dermomyotome. Back muscles ○ These proteins induce expression of MYF5 and MyoD Innervated by dorsal primary rami Members of a family of transcription factors ○ Hypomeric rami called myogenic regulatory factors (MRFS) - Muscles of the limb and body wall group of genes that activates pathways for Innervated by ventral primary rami muscle development The new description is based on the actual embryological origin of muscle cells from two different populations of muscle cell precursors, the abaxial and primaxial cells, and not their innervation. ○ Does not preclude the fact that epaxial (above the axis) muscles (back muscles) are innervated by dorsal primary rami, whereas hypaxial (below the axis) muscles (body wall and limb muscles) are innervated by ventral primary rami. Figure 3. Expression patterns of genes that regulate somite differentiation. 1. SHH and noggin → cause the ventral part of the somite to form sclerotome and to express PAX1 2. PAX1 → controls chondrogenesis and vertebral formation. 3. WNT and SHH proteins → activate PAX3 4. PAX3 → demarcates the dermatome 5. WNT proteins → direct the DML portion of the somite to form muscle precursor cells and to express the muscle-specific gene MYF5. 6. Dermatome portion of the somite → become dermis directed by neurotrophin 3 (NT-3) secreted by the dorsal neural tube. 7. The combined influence of activating WNT proteins and inhibitory Figure 2. Cross section through half the embryo showing innervation to BMP4 protein activates MyoD expression in the Ventrolateral (VLL) developing musculature. Epaxial (true back muscles) are innervated by dorsal region to create a second group of muscle cell precursors. (posterior) primary rami. Hypaxial muscles (limb and body wall) are innervated by ventral (anterior) primary rami. VI. HEAD MUSCULATURE IV. SKELETAL MUSCLE AND TENDONS All voluntary muscles of the head region are derived from paraxial mesoderm (somitomeres and somites), including musculature of the During differentiation, precursor cells, the myoblasts, fuse and form tongue, eye (except that of the iris, which is derived from optic cup long, multinucleated muscle fibers ectoderm), and that associated with the pharyngeal (visceral) arches ○ Myofibrils soon appear in the cytoplasm, and by the end (refer to table 2 and figure 4). of the third month, cross-striations, typical of skeletal Patterns of muscle formation in the head are directed by connective muscle, appear. tissue elements derived from neural crest cells. ○ Tendons are derived from sclerotome cells lying adjacent to myotomes at the anterior and posterior borders of the somites. Page 2 of 5 [EMBRYOLOGY] 1.08 EMBRYONIC DEVELOPMENT OF THE MUSCULAR SYSTEM – Dr. Modesto David A. Bolislis, MD In gut wall and its derivatives: ○ Smooth muscle derived from splanchnic (visceral) layer of lateral plate mesoderm Sphincter and dilator muscles of the pupil and muscle tissue in the mammary and sweat glands ○ Derived from ectoderm Serum Response Factor (SRF) ○ Transcription factor responsible for smooth muscle differentiation. ○ This factor is upregulated by growth factors through Table 2. Origins of the Craniofacial Muscles. aSomites 2 to 5 constitute the kinase phosphorylation pathways. occipital group [somite 1 degenerates for the most part]. ○ Myocardin and myocardin-related transcription factors (MRTFs) VII. LIMB MUSCULATURE act as coactivators to enhance the activity of SRF → Initiation of the genetic cascade responsible for smooth muscle development. The first indication of limb musculature is observed in the seventh week of development as a condensation of mesenchyme near the base of the limb buds (refer to figure 4). X. CLINICAL CORRELATIONS The mesenchyme is derived from dorsolateral cells of the somites that migrate into the limb bud to form the muscles. Poland Sequence Connective tissue ○ Occurs in 1 per 20,000 individuals ○ dictates the pattern of muscle formation ○ Characterized by absence of the pectoralis minor and ○ derived from the parietal layer of lateral plate mesoderm, partial loss of the pectoralis major [usually the sternal which also gives rise to the bones of the limb head] muscles. ○ The nipple and areola are absent or displaced, and there are often digital defects on affected side: syndactyly - fused digits brachydactyly - short digits ○ The disfiguring nature of the defects can be problematic, especially in females because of breast development. Figure 4. Drawing showing musculature in the head and neck derived from somitomeres and myotomes that form from the occipital region caudally in a 7-week embryo. VIII. CARDIAC MUSCLE Cardiac muscle develops from splanchnic (visceral) mesoderm surrounding the endothelial heart tube. Myoblasts ○ Adhere to one another by special attachments that later develop into intercalated discs Myofibrils ○ Develop as a skeletal muscle but they will not fuse Figure 5.. Poland sequence. The pectoralis minor and part of the pectoralis Purkinje fibers major muscles are missing on the patient’s left side. Note displacement of the ○ few special bundles of muscle cells with irregularly nipple and areola. distributed myofibrils formed during later development ○ Fibers responsible for conduction system of the heart Prune Belly Syndrome ○ Partial or complete absence of abdominal musculature; abdominal wall is so thin that organs are visible and easily IX. SMOOTH MUSCLE palpated. ○ Malformations of the urinary tract and bladder, including urethral obstruction. Smooth muscle for dorsal aorta and large arteries is derived from ○ These defects cause an accumulation of fluid that lateral plate mesoderm and neural crest cells. distends the abdomen, resulting in atrophy of the In coronary arteries: abdominal muscles. ○ Smooth muscle originates from proepicardial cells and neural crest cells (proximal segments). Page 3 of 5 [EMBRYOLOGY] 1.08 EMBRYONIC DEVELOPMENT OF THE MUSCULAR SYSTEM – Dr. Modesto David A. Bolislis, MD ○ Signals from lateral plate mesoderm (BMP) and overlying ectoderm (WNT) induce VIL ○ Signals from neural tube and notochord (SHH and WNT) induce DML cells. ○ Connective tissue derived from smites, parietal mesoderm and neural crest (head region) provides a template for establishment of muscle patterns. ○ Most smooth muscles and cardiac muscles are derived from mesoderm. ○ Smooth muscles of the pupil, mammary gland and sweat glands differentiate from ectoderm Figure 6.. Prune belly syndrome: a distended abdomen from atrophy of abdominal wall musculature. TEST YOUR KNOWLEDGE Muscular dystrophy 1. Muscle cells are derived from what two regions of the somite? ○ Term for a group of inherited muscle diseases that cause a. Muscle cells are derived from the ventrolateral and progressive muscular wasting and weakness. dorsomedial edges of the somites. ○ Duchenne muscular dystrophy (DMD) b. Muscle cells are derived from the dorsolateral and most common (1 per 4,000 male births). ventromedial edges of the somites. inherited as X-linked recessive such that males c. Muscle cells are derived from the ventroposterior and are much more often affected than females. dorsomedial lips of the somites. ○ Both DMD and Becker muscular dystrophy [BMD] are d. Muscle cells are derived from the ventrolateral and caused by mutations in the gene for dystrophin on the X dorsoanterior lips of the somites. chromosome. However, in DMD, no functional dystrophin 2. Which region contributes to the abaxial mesodermal domain? is made, and the disease is much more severe with an a. Lateral plate mesoderm earlier onset (