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Presenting Author(s) Heidi Bildsoe
Abstract Title Hedgehog can directly drive terminal differentiation of amniote skeletal muscle.
Full author List Heidi Bildsoe Xiaopeng Li, Christopher S. Blagden, Marie Ange Bonnin, Delphine Duprez and Simon M. Hughes.
Text of abstract

Hedgehog (Hh) signalling is involved in anteroposterior patterning and maintenance of the apical ectodermal ridge in the early limb. Hh may also have later functions in myogensis. However, it is unclear which Hh-responses are the direct result of Hh action on myogenic cells because Hhs frequently elicit secondary signals. Hhs promote slow myogenesis in zebrafish and are involved in specification of medial muscle cells in amniote somites. But the extent to which non-myogenic cells, myoblasts or differentiating myocytes are direct or indirect targets of Hh signalling is not known. We show that Sonic hedgehog (Shh) can act directly on cultured myoblasts, driving Gli1 expression, myogenin up-regulation and terminal differentiation, even in the presence of growth factors that normally prevent differentiation. Distinct myoblasts respond differently to Shh: in some slow myosin expression is increased, whereas in others Shh simply enhances terminal differentiation.

Exposure of chick wing bud cells to Shh in culture increases numbers of both muscle and non-muscle cells, yet simultaneously enhances differentiation of myoblasts. The small proportion of differentiated muscle cells expressing slow myosin can be doubled by Shh. Shh over-expression in chick limb bud reduces muscle mass at early developmental stages while inducing ectopic slow muscle fibre formation. Abundant later-differentiating fibres, however, do not express extra slow myosin. Conversely, Hh loss of function in the limb bud, caused by implanting hybridoma cells expressing a functionally blocking anti-Hh antibody, reduces early slow muscle formation and differentiation, but does not prevent later slow myogenesis. Analysis of Hh knockout mice indicates that Shh promotes early somitic slow myogenesis. Taken together, the data show that Hh can have direct pro-differentiative effects on myoblasts and that early-developing muscle requires Hh for normal differentiation and slow myosin expression. We propose a simple model in which, in addition to the early limb patterning effects of Hedgehog signalling, direct and indirect effects of Hh regulate early limb myogenesis.

Which session is your work most relevant to: Tissue differentiation