Atit Radhika, Sgaier Sema K, Mohamed Othman A, Taketo Makoto M, Dufort Daniel, Joyner Alexandra L, Niswander Lee, Conlon Ronald A
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
Dev Biol. 2006 Aug 1;296(1):164-76. doi: 10.1016/j.ydbio.2006.04.449. Epub 2006 Apr 21.
Dorsal dermis and epaxial muscle have been shown to arise from the central dermomyotome in the chick. En1 is a homeobox transcription factor gene expressed in the central dermomyotome. We show by genetic fate mapping in the mouse that En1-expressing cells of the central dermomyotome give rise to dorsal dermis and epaxial muscle and, unexpectedly, to interscapular brown fat. Thus, the En1-expressing central dermomyotome normally gives rise to three distinct fates in mice. Wnt signals are important in early stages of dermomyotome development, but the signal that acts to specify the dermal fate has not been identified. Using a reporter transgene for Wnt signal transduction, we show that the En1-expressing cells directly underneath the surface ectoderm transduce Wnt signals. When the essential Wnt transducer beta-catenin is mutated in En1 cells, it results in the loss of Dermo1-expressing dorsal dermal progenitors and dermis. Conversely, when beta-catenin was activated in En1 cells, it induces Dermo1 expression in all cells of the En1 domain and disrupts muscle gene expression. Our results indicate that the mouse central dermomyotome gives rise to dermis, muscle, and brown fat, and that Wnt signalling normally instructs cells to select the dorsal dermal fate.
在鸡中，背部真皮和轴上肌已被证明起源于中央皮肌节。En1是一种在中央皮肌节中表达的同源框转录因子基因。我们通过在小鼠中的遗传命运图谱研究表明，中央皮肌节中表达En1的细胞产生背部真皮、轴上肌，并且出乎意料的是，还产生肩胛间棕色脂肪。因此，在小鼠中，表达En1的中央皮肌节通常会产生三种不同的细胞命运。Wnt信号在皮肌节发育的早期阶段很重要，但尚未确定决定真皮命运的信号。使用Wnt信号转导的报告转基因，我们发现表面外胚层正下方表达En1的细胞可转导Wnt信号。当在En1细胞中必需的Wnt转导蛋白β-连环蛋白发生突变时，会导致表达Dermo1的背部真皮祖细胞和真皮缺失。相反，当在En1细胞中激活β-连环蛋白时，它会在En1结构域的所有细胞中诱导Dermo1表达，并破坏肌肉基因表达。我们的结果表明，小鼠中央皮肌节可产生真皮、肌肉和棕色脂肪，并且Wnt信号通常指导细胞选择背部真皮命运。
