Sonic hedgehog is a survival factor for hypaxial muscles during mouse development

Sonic hedgehog (Shh) has been proposed to function as an inductive and trop hic signal that controls development of epaxial musculature in vertebrate e mbryos, In contrast, development of hypaxial muscles was assumed to occur i ndependently of Shh, We here show that formation of limb muscles was severe ly affected in two different mouse strains with inactivating mutations of t he Shh gene. The limb muscle defect became apparent relatively late and ini tial stages of hypaxial muscle development were unaffected or only slightly delayed, Micromass cultures and cultures of tissue fragments derived from limbs under different conditions with or without the overlaying ectoderm in dicated that Shh is required for the maintenance of the expression of myoge nic regulatory factors (MRFs) and, consecutively, for the formation of diff erentiated limb muscle myotubes. We propose that Shh acts as a survival and proliferation factor for myogenic precursor cells during hypaxial muscle d evelopment. Detection of a reduced but significant level of Myf5 expression in the epaxial compartment of somites of Shh homozygous mutant embryos at E9.5 indicated that Shh might be dispensable for the initiation of myogenes is both in hypaxial and epaxial muscles. Our data suggest that Shh acts sim ilarly in both semitic compartments as a survival and proliferation factor and not as a primary inducer of myogenesis.