Sonic Hedgehog Inhibits the Terminal Differentiation of Limb Myoblasts Committed to the Slow Muscle Lineage

Abstract

The proliferation, differentiation, and fusion of a small number of myogenic precursor cells must be precisely regulated during development to ensure the proper size, organization, and function of the limb musculature. We have examined the role of Sonic hedgehog (Shh) in these processes by both augmentation and inhibition of the Shh-mediated signaling pathway. Our data show that Shh regulates muscle development by repressing the terminal differentiation of early myogenic precursor cells and does not function as a myoblast mitogen. Shh function in hypaxial muscle appears to be spatially restricted to the early myoblast population within the ventral muscles of the posterior region of the limb. Furthermore, Shh appears to act as a permissive, rather than an inductive, signal for slow MyHC expression in myoblasts. Our data thus provide the foundation for a new hypothesis for Shh function in hypaxial skeletal muscle development.

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

“…Interestingly, however, our findings are consistent with inhibitory effects of Shh on muscle differentiation observed in other experimental conditions (Bren-Mattison and Olwin, 2002). One explanation of these discrepancies is that the effects of the Hh signal on muscle differentiation in vivo are likely to vary with timing and level of Hh signaling (Wolff et al, 2003).…”

Normal and aberrant craniofacial myogenesis by grafted trunk somitic and segmental plate mesoderm

“…The possibility that the second arch environment may differ in the spatiotemporal distribution of other myogenic factors, e.g. sonic hedgehog (Bren-Mattison and Olwin, 2002) or noggin and gremlin, from migrating crest cells (Tzahor et al, 2003) cannot be excluded.…”

Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice

“…In zebrafish embryos, the Sonic hedgehog (Shh) signaling pathway determines the slow muscle fiber lineage (Blagden et al, 1997;Norris et al, 2000;Barresi et al, 2000;Baxendale et al, 2004). However, in higher vertebrates such as chickens, Shh does not initiate slow muscle fiber differentiation (Duprez et al, 1998;Cann et al, 1999;Bren-Mattison and Olwin, 2002).…”