Brownian Motion
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W
ith the exception of some smooth muscle tissue (see later), the muscu-lar system develops from the meso-dermal germ layer and consists of skeletal, smooth, and cardiac muscle. Skeletal muscle is derived from paraxial mesoderm, which forms somites from the occipital to the sacral regions and somitomeres in the head. Smooth muscle differentiates from visceral splanchnic mesoderm surrounding the gut and its deriva-tives and from ectoderm (pupillary, mammary gland, and sweat gland muscles). Cardiac muscle is derived from visceral splanchnic mesoderm surrounding the heart tube.STRIATED SKELETAL MUSCULATURE
Head musculature (see Chapter 17) is derived from seven somitomeres, which are par-tially segmented whorls of mesenchymal cells derived from paraxial mesoderm (see Chapter 6, p. 72). 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. Immediately after segmentation, these somitomeres undergo a process of epitheliza-tion and form a “ball” of epithelial cells with a small cavity in the center (Fig. 11.1A). The ventral region of each somite then becomes mesenchymal again and forms the sclero-tome (Fig. 11.1B–D), the bone-forming cells for the vertebrae and ribs. Cells in the upper region of the somite form the dermatome and two muscle-forming areas at the ventrolateral (VLL) and dorsomedial (DML) lips (or edges), respectively (Fig. 11.1B). Cells from these two areas migrate and proliferate to form progeni-tor muscle cells ventral to the dermatome, thereby forming the dermomyotome (Figs.
11.1B,C and 11.2). Some cells from the VLL region also migrate into the adjacent parietal layer of the lateral plate mesoderm (Fig. 11.1B).
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146 Part II Systems-Based Embryology
A B
C D
Neural groove
Ventral
somite wall Notochord
Intra-embryonic
cavity
Sclerotome Lateral
somitic frontier
Sclerotome
Sclerotome
Dermatome Dermatome
Myotome
Neural tube
Dorsal aorta
Neural tube Dorsomedial muscle cells Dermatome Ventrolateral muscle cells
Figure 11.1 Cross-sectional drawings showing the stages of development in a somite. A. Mesoderm cells become epithelial and are arranged around a small lumen. B. Cells in the ventral and medial walls of the somite lose their epithelial characteristics and migrate around the neural tube and notochord, and some move into the parietal layer of lateral plate mesoderm. Collectively, these cells constitute the sclerotome. Cells at the DML and VLL regions of the somite form muscle cell precursors. Cells from both regions migrate ventral to the dermatome to form the dermomyotome. VLL cells also migrate into the parietal layer of lateral plate mesoderm across the lateral somitic frontier (green line). In combination, somitic cells and lateral plate mesoderm cells constitute the abaxial mesodermal domain, while the primaxial mesodermal domain only contains somitic cells (paraxial mesoderm).
C. Together, dermatome cells and the muscle cells that associate with them form the dermomyotome. D. The dermomyotome begins to differentiate: Myotome cells contribute to primaxial muscles, and dermatome cells form the dermis of the back.
INNERVATION OF AXIAL SKELETAL MUSCLES
The new description of muscle development characterized by primaxial and abaxial domains differs from the old concept of epimeres (back muscles) and hypomeres (limb and body wall muscles), which was based on a functional defi -nition of innervation: Epimeric muscles were innervated by dorsal primary rami; hypomeric muscles by ventral primary rami. The new description is based on the actual embryo-logical origin of muscle cells from two dif-ferent populations of muscle cell precursors, the abaxial and primaxial cells, and not their
Occipital myotomes Cervical
myotomes
Thoracic myotomes
T1
C1
I IVIII
II
Pharyngeal arch muscles
Eye muscles
Eye Limb axis Mesenchymal
condensation of limb bud
Epithelial ridge
Figure 11.2 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.
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Chapter 11 Muscular System 147
innervation. The description does not pre-clude 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 (Fig. 11.4).
Dermis
MYF5
MYOD
WNT
SHH NOGGIN PAX1 WNT
BMP4 Muscle PAX3
cells
Muscle cells
NT-3
BMP4
Figure 11.3 Expression patterns of genes that regulate somite differentiation. Sonichedgehog (SHH) and nog-gin, secreted by the notochord and fl oor plate of the neural tube, cause the ventral part of the somite to form sclerotome and to express PAX1, which in turn controls chondrogenesis and vertebral formation. WNT and low concentrations of SHH proteins from the dorsal neural tube activate PAX3, which demarcates the dermatome.
WNT proteins also direct the DML portion of the somite to form muscle precursor cells and to express the muscle-specifi c gene MYF5. The dermatome portion of the somite is directed to become dermis by neurotrophin 3 (NT-3) secreted by the dorsal neural tube. The combined infl u-ence of activating WNT proteins and inhibitory BMP4 pro-tein activates MyoD expression in the Ventrolateral (VLL) region to create a second group of muscle cell precursors.
Back (epaxial) muscles
Dorsal primary ramus Ventral primary
ramus Body wall
muscles
Hypaxial muscles
Flexor muscle of limb
Extensor muscle
of limb
Figure 11.4 Cross section through half the embryo showing innervation to developing musculature. Epaxial (true back muscles) are innervated by dorsal (posterior) primary rami. Hypaxial muscles (limb and body wall) are innervated by ventral (anterior) primary rami.
TABLE 11.1 Origins of Muscles from Abaxial and Primaxial Precursors
Primaxial Abaxial
Cervical region Scalenes Infrahyoid
Geniohyoid Prevertebral
Thoracoabdominal region Intercostals Pectoralis major and minor External oblique
Internal oblique Transversus abdominus Sternalis
Rectus abdominus Pelvic diaphragm
Upper limb Rhomboids Distal limb muscles
Levator scapulae Latissimus dorsi
Lower limba All lower limb muscles
aThe precise origin of muscles in the pelvic region and lower limb has not been determined, but most if not all are abaxial in origin.
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and this group of genes activates pathways for muscle development.
PATTERNING OF MUSCLES
Patterns of muscle formation are controlled by connective tissue into which myoblasts migrate.
In the head region, these connective tissues are derived from neural crest cells; in cervical and occipital regions, they differentiate from somitic mesoderm; and in the body wall and limbs, they originate from the parietal layer of lateral plate mesoderm.
HEAD MUSCULATURE
All voluntary muscles of the head region are derived from paraxial mesoderm (somitomeres and somites), including musculature of the tongue, eye (except that of the iris, which is derived from optic cup ectoderm), and that associated with the pharyngeal (visceral) arches (Table 11.2, p. 146, and Fig. 11.2). Patterns of muscle formation in the head are directed by connective tissue ele-ments derived from neural crest cells.
LIMB MUSCULATURE
The fi rst indication of limb musculature is observed in the seventh week of development as a condensation of mesenchyme near the base of the limb buds (Fig. 11.2). The mesenchyme is derived from dorsolateral cells of the somites that migrate into the limb bud to form the muscles.
As in other regions, connective tissue dictates the pattern of muscle formation, and this tissue is derived from the parietal layer of lateral plate mesoderm, which also gives rise to the bones of the limb (see chapter 12).
SKELETAL MUSCLE AND TENDONS
During differentiation, precursor cells, the myo-blasts, fuse and form long, multinucleated muscle fi bers. Myofi brils soon appear in the cytoplasm, and by the end of the third month, cross-striations, typical of skeletal muscle, appear. A similar pro-cess occurs in the seven somitomeres in the head region rostral to the occipital somites. However, somitomeres never segregate into recognizable regions of sclerotome and dermomyotome seg-ments prior to differentiation. Tendons for the attachment of muscles to bones are derived from sclerotome cells lying adjacent to myotomes at the anterior and posterior borders of somites.
The transcription factor SCLERAXIS regulates development of tendons.
MOLECULAR REGULATION OF MUSCLE DEVELOPMENT
Genes regulating muscle development have recently been identifi ed. Bone morphogenetic protein 4 (BMP4) and probably fi broblast growth factors from lateral plate mesoderm, together with WNT proteins from adjacent ectoderm, signal VLL cells of the dermomyotome to express the muscle-specifi c gene MyoD (Fig. 11.3). BMP4 secreted by ectoderm cells induces production of WNT proteins by the dorsal neural tube at the same time that low concentrations of sonic hedgehog (SHH) proteins, secreted by the noto-chord and fl oor plate of the neural tube, reach the DML cells of the dermomyotome. Together these proteins induce expression of MYF5 and MyoD in these cells (note that SHH does not play a role in specifying VLL cells). Both MyoD and MYF5 are members of a family of transcription factors called myogenic regulatory factors (MRFs),
TABLE 11.2 Origins of the Craniofacial Muscles
Mesodermal Origin Muscles Innervation
Somitomeres 1 and 2 Superior, medial, ventral recti Oculomotor (III)
Somitomere 3 Superior oblique Trochlear (IV)
Somitomere 4 Jaw closing Trigeminal (V)
Somitomere 5 Lateral rectus Abducens (VI)
Somitomere 6 Jaw opening, other second arch Facial (VII)
Somitomere 7 Stylopharyngeus Glossopharyngeal (IX)
Somites 1 and 2 Intrinsic laryngeals Vagus (X)
Somites 2–5a Tongue Hypoglossal (XII)
aSomites 2 to 5 constitute the occipital group (somite 1 degenerates for the most part).
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