Myogenic determination occurs independently in somites and limb buds

Gene targeting has indicated that the bHLH transcription factors Myf-5 and MyoD are required for myogenic determination because skeletal myoblasts and myofibers are entirely ablated in mouse embryos lacking both Myf-5 and Myo D. Entrance into the skeletal myogenic program during development occurs fo llowing the independent transcriptional induction of either Myf-5 or MyoD. To identify sequences required for the de novo induction of MyoD transcript ion during development, we investigated the expression patterns of MyoD-lac Z transgenes in embryos deficient in both Myf-5 and MyoD. We observed that a 258-bp fragment containing the core of the -20-kb MyoD enhancer activated expression in newly formed somites and limb buds in compound mutant embryo s lacking both Myf-5 and MyoD. Importantly, Myf-5- and Myo-Ddeficient presu mptive muscle precursor cells expressing beta-galactosidase were observed t o assume nonmuscle fates primarily as precartilage primordia in the trunk a nd the limbs, suggesting that these cells were multipotential. Therefore, c ells are recruited into the MpoD-dependent myogenic lineage through activat ion of the -20-kb MyoD enhancer and this occurs independently in somites an d limb buds. (C) 1999 Academic Press.