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 MyoD. Entrance into the skeletal myogenic program during development occurs following the independent transcriptional induction of either Myf-5 or MyoD. To identify sequences required for the de novo induction of MyoD transcription during development, we investigated the expression patterns of MyoD-lacZ 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 embryos lacking both Myf-5 and MyoD. Importantly, Myf-5- and MyoD-deficient presumptive muscle precursor cells expressing beta-galactosidase were observed to assume nonmuscle fates primarily as precartilage primordia in the trunk and the limbs, suggesting that these cells were multipotential. Therefore, cells are recruited into the MyoD-dependent myogenic lineage through activation of the -20-kb MyoD enhancer and this occurs independently in somites and limb buds.
Kablar
B
B
Institute for Molecular Biology and Biotechnology, Cancer Research Group, McMaster University, Hamilton, Ontario, L8S 4K1, Canada.
Krastel
K
K
Ying
C
C
Tapscott
S J
SJ
Goldhamer
D J
DJ
Rudnicki
M A
MA
D000818:Animals; D002465:Cell Movement; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D019170:Somites / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators