Characterisation of the MRFs and role of FGF18 in vertebrate limb myogenesis

• Main Author: Mok, Gi Fay
• Published: University of Nottingham 2014
• Subjects: 573.7
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662208

In vertebrates, all trunk muscles, which includes the body and limb muscles, are derived from muscle progenitor cells originating in somites. Somites are segmentally repeated embryonic epithelial balls of cells that bud off from the pre-segmented paraxial mesoderm in a rostral -caudal progression along either side of the neural tube (Brand -Saberi et al., 1996, Dequeant and Pourquie, 2008, Pourquie, 2011) . During embryonic development, somites mature and differentiate into a variety of distinct tissues: a) the sclerotome, that gives rise to the vertebrae bone, connective tissue and cartilage surrounding neural structures; b) the dermomyotome, that gives rise to muscle progenitors, dermis and angiogenic cells; c) the syndetome, from which axial tendons are derived and d) the myotome, which is where muscle differentiation first occurs in the embryo. Limb muscles originate from somites only at limb -level and the formation of muscle involves several steps: migration, proliferation and differentiation (Duprez, 2002). At limb level, progenitor cells at the ventro-lateral lip of the dermomyotome delaminate and migrate into the limb bud. Delamination and migration occurs when a signal from the limb bud, HGF (hepatocyte growth factor)/SF (scatter factorL produced by mesodermal cells from the limb bud, interacts with C-met, a tyrosine kinase receptor expressed in the muscle progenitor cells localised at the ventro- Iateral lip (Dietrich et al., 1998). The progenitors migrate to two distinct regions in the limb: the dorsal muscle mass and the ventral muscle mass. Only at these two regions do the progenitor cells activate the myogenic programme and express muscle-specific genes such as the myogenic regulatory factors (MRFs). At transcriptional level, there are four key myogenic genes that have been implicated to be important for trunk muscle formation. These are the MRFs, a group of four basic helix-loop- helix transcription factors which includes MyfS, MyoD, myogenin and MRF4 (also known as Myf6). Although the first MRF was described back in 1987 (Davis et al., 1987L and the first in situ hybridisation experiments were performed using radioactive -labelled probes (Pownall and Emerson, 1992), the expression profile for the MRFs during embryogenesis was not comprehensive and remained fragmented in both chick and mouse.