Time period: day 22 to week 9
Most muscle cells originate from the paraxial mesoderm (Figure 25.1), and specifically the myotome portion of the somites. The three types of muscle described here are skeletal, smooth and cardiac muscle.
Within each somite the myotome splits into two muscle‐forming parts: a ventrolateral edge and a dorsomedial edge (Figures 25.2 and 25.3). The ventrolateral edge cells will form the hypaxial musculature (i.e. that of the ventral body wall and, in the limb regions, musculature of the limbs) (Figures 25.4 and 25.5). The dorsomedial edge will form the epaxial musculature (the back muscles).
During formation of skeletal muscle multiple myoblasts (muscle precursor cells) fuse to form myotubes at first, and then long multi-nucleated muscle fibres (Figure 25.6). By the end of month 3, microfibrils have formed and the striations of actin and myosin patterning associated with skeletal muscle are visible. Important genes involved in myogenesis include MyoD and Myf5, which cause mesodermal cells to begin to differentiate into myoblasts, and then MRF4 and Myogenin later in the process.
A fourth part of the somite, the syndetome, has been recently shown to contain precursor cells of tendons (Figures 25.2 and 25.3). The cells of the syndetome lie at the ventral and dorsal edges of the somites between the cells of the myotome and sclerotome; blocks of cells whose tissues they will connect. They also migrate, but develop independently of muscles and connect later in development. However, tendon cells will also arise from lateral plate mesoderm to populate the limbs, so the full story of tendon development is not limited to the somite.
The upper limb bud is visible from day 26 around the levels of cervi- cal somite 5 to thoracic somite 3. The lower limb starts at the level of lumbar somite 2 and finishes between lumbar 5 and sacral 2 (see Figure 26.1). The migrating muscle precursors migrate into the limbs, coalesce and form specific muscle masses which then split to form the definitive muscles of the limbs (see Chapter 26). It is known that, as in skeletal development, cell death is important in the development of these muscle masses. Joints within the limbs develop independently from the musculature (see Chapter 23) but foetal musculature and the motions that occur are required to retain the joint cavities.
Neurons of spinal nerves that follow migrating myoblasts are specific to their original segmental somites. By roughly 9 weeks most muscle groups have formed in their specific locations. The migration of whole myotomes and fusion between them accounts for the grouping of muscular innervation seen in adult limb anatomy.
Movements of the limbs can be detected using ultrasound at 7 weeks and isolated limb movements from around 10–11 weeks.
In the head area the somitomeres undergo similar changes but never fully develop the three compartments of the somite, and this process remains less well understood.
Myogenesis in the head differs from trunk and limb myogenesis as these muscles have different phenotypic properties, although myoblasts still develop from the paraxial mesoderm of the somitomeres and migrate into the pharyngeal arches and their terminal locations.
The surrounding connective tissues coordinate migration and differentiation of muscle as elsewhere, but the nerves to these muscles are present before their formation, as they are cranial nerves. Musculature formed from pharyngeal arches and their innervation is described in Chapters 40–43.
Extraocular muscles probably arise from mesenchyme near the prechordal plate (a thickening of endoderm in the embryonic head). Muscles of the iris are derived from neuroectoderm, whereas ciliary muscle is formed by lateral plate mesoderm. Muscles of the tongue form from occipital somites, as does the musculature of the pharynx. Movement of the mouth and tongue and the ability to swallow amniotic fluid begins around week 12.
Most smooth muscle of the viscera and gastrointestinal tract (Figure 25.7) is derived from splanchnic mesoderm that is located where the organs are developing (Figure 25.8). Developing blood vessels surround local mesenchyme that forms smooth muscle. Larger blood vessels (aorta and pulmonary vessels) receive contributions from neural crest cells.
Exceptions to the splanchnic mesoderm rule include muscles of the pupil, erector pili muscles of hair, salivary glands, lacrimal glands, sweat glands and mammary gland smooth muscle, all of which are derived from ectoderm.
Cardiac muscle cells are also derived from splanchnic mesoderm surrounding the early heart tube. The cardiac myoblasts differ from skeletal myoblasts in that they do not fuse to form multinucleated fibres, and they remain individual but connected via intercalated discs (Figure 25.9).
At approximately 22 days a cardiac tube has formed that can contract (see Chapter 27).
Muscular dystrophy is a group of over 20 muscular diseases that have genetic causes and all produce progressive weakness and wasting of muscular tissue.
Duchenne muscular dystrophy affects boys (in extremely rare cases symptoms show in female carriers) and affects the gene coding for the protein dystrophin. Patients develop problems with walking between 1 and 3 years of age, wheelchairs are necessary between 8 and 10 years, and life expectancy is limited to late teens to early adulthood as cardiac muscle is affected in the later stages of the disease. There is no cure but research into using stem cells in forms treatment is ongoing.
An absence or partial absence of a skeletal muscle can occur (e.g. Poland anomaly which exhibits a unilateral lack of pectoralis major). Other commonly affected muscles include quadriceps femoris, serratus anterior, l and palmaris longus, and are relatively common.