Review Article

Gene Networks during Skeletal Myogenesis

Figure 1

Skeletal myogenesis. (a) Induction of Myogenesis. Somites form in a rostral to caudal manner as a result of segmentation of the paraxial mesoderm. They lie on each side of the neural tube and notochord and are the source of body musculature. As somites mature, they receive signals from the adjacent neural tube (NT) and notochord (NC). These signals result in the division of the somite into the sclerotome (S), dermomyotome (DM), and myotome (M). Cells in the epaxial region will give rise to the muscles of the deep back, while cells in the hypaxial region will give rise to the muscles of the abdomen and limbs. Shh from the floor plate of the neural tube and from the notochord and Wnt1 from the dorsal neural tube activate Myf5, which in turn activates Myod. Wnt7 and Pax3 from the dorsal neural tube also activate Myod to initiate myogenesis of the epaxial somites. Activation of Pax3, by Pitx2 and Six/Eya, activates Myf5 and Myod for initiation of hypaxial myogenesis. (b) Gene Regulatory Networks. Interactive networks of SSTFs in anatomically distinct muscle groups as modeled in biotapestry [78]. Developmental networks regulating myogenesis depend on the anatomical location of the myogenic population. The MRFs are universal nodes in muscle development, but the upstream effectors are what define each population. Myogenesis of the head and neck depends on MyoR and Pitx2 and is distinct from the myogenesis of the trunk which all depends on the genes Six1/4 or Eya1/2. Within the trunk, the abdomen, limb, and back can be considered distinct regulatory regions, each with their own set of upstream regulators. Green arrows indicate a positive downstream effect, while red arrows indicate a negative downstream effect. (c) Contractile Apparatus of the Muscle. Myoblasts fuse to form a multinucleated muscle fiber, the smallest complete contractile system. Muscle fibers or muscle cells consist of many contractile unites, the myofibrils. Myofibrils consist of an ordered arrangement of long molecules, the thick (myosin) and thin (actin) myofilaments, which one called sarcomeres. Myosin is responsible for force generation. Actin is responsible for motion generation. Titin maintains the order of the striation patterning by anchoring the myosin network to the actin network.
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