CNRS URA 2578, Département de Biologie du Développement, Institut Pasteur, 75015 Paris, France.
Dev Cell. 2009 Dec;17(6):892-9. doi: 10.1016/j.devcel.2009.10.021.
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.
多能性的维持以及细胞如何退出这种状态并采取特定命运是干细胞生物学中的核心问题。在脊椎动物发育过程中,背侧体节的多能细胞,即真皮肌节,分别产生不同的谱系,如血管平滑肌和骨骼肌肉,分别受转录因子 Foxc2 和 Pax3 的调节。在这里,我们在小鼠胚胎中显示了 Pax3 和 Foxc2 之间的相互抑制。通过遗传方法和体节外植体中外部信号的操纵,我们证明了 Pax3:Foxc2 比值调节成肌细胞与血管细胞命运。这为我们提供了深入了解这些真皮肌节谱系基因如何协调细胞命运选择的线索。