Immunohistochemical stain ANT (green), Mitotracker (red)
Muscle Determinaton, Proliferation, Differentiation and Maturation
Originate in Dermatomytotome, which differentiates into dermatome and myotome as somites divide and mature. SKM derives from Myoblasts, populating the myotome.Genes involved in myogenic differentiation:
MyoD, myogenin, myf5, MRF4/herculin. Genes that code for basic helix-loop-helix (HL) family of transcriptional activators that are SKM specific and bind to regulatory domain of many SKM-specific domain. In mice, myf5 is expressed as one of the earliest SKM-specific gene detectable. Myogenin assoc. with myoblast fusion and differentiation. Differentiation repressed by peptide hormones, notable FGF and Transforming growth factor B (TFGF-B) and products of proto-oncogenes (RAS). Primary and secondary myotubes. Primary myotubes provide scaffolding for secondary myotubes. Secondary form on surface of primaries beneath the basal lamina. In primaries, slow, heavy chain myosin expressing (MHCbeta), embryonic MHC (MHCemb) and sometimes low amounts of perinantal (MHCpn) are expressed. Secondaries only MHCemb and MHCpn. Primaries are nerve independent, whereas secondaries are nerve dependent. Differences are due to expression of multiple isoforms. Multigene Families (MHC and actin), or alternative splicing (Myosin light chain, MLC; troponin, tropomyosin). MHC: cardiac isoforms MHCa, MHCb. Adult fast SKM (MHCIIa and MHCIIb), Adult slow SKM (MHCb), Extraocular muscle (MHCeo) and developing SKM (MHCemb,MHCpn,MHCb). 4 MLC genes are expressed in rodents: MLC1F, MLC3F in adult fast SKM, MLC1V and MLC1A are cardiac isoforms also expressed in adult slow and fetal SKM. SKM fiber characteristics define by coordinated expression of appropriate isoforms of SKM-specific genes. General agreement, that final expression pattern is result of environmental or extrinsic factors, principally inervation and the influence of hormones and growth factors.. Mouse muscle fiber differentiation is complete by birth.. Period of muscle growth and maturation ranges from 4-16 weeks in rats. During this period, muscle becomes invervated by branches from spinal nerves.