Maintenance of multipotency and how cells exit this state to adopt a specific fate are central questions in stem cell biology. During vertebrate development, multipotent cells of the dorsal somite, the dermomyotome, give rise to different lineages such as vascular smooth and skeletal muscle, regulated by the transcription factors Foxc2 and Pax3, respectively. Here we show reciprocal inhibition between Pax3 and Foxc2 in the mouse embryo. Using both genetic approaches and manipulation of external signals in somite explants, we demonstrate that the Pax3:Foxc2 ratio modulates myogenic versus vascular cell fates. This provides insight into how cell fate choices are orchestrated by these lineage genes in the dermomyotome.
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