Jiang L I, Sternberg P W
Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125 USA.
Genes Dev. 1999 Apr 1;13(7):877-89. doi: 10.1101/gad.13.7.877.
We show that during Caenorhabditis elegans male spicule development, the specification of a glial versus neuronal cell fate in a canonical neurogenic sublineage is dependent on Wnt signaling. Inactivation of a Wnt signaling pathway mediated by the Wnt receptor LIN-17 transforms the SPD sheath cell into its sister, the SPD neuron. We discovered a new mutant, son-1, that displays this same cell fate transformation. The son-1 mutation enhances the phenotypes of reduction-of-function lin-17 mutants in several developmental processes, including vulva development, somatic gonad development, and male tail patterning. son-1 encodes an HMG1/2-like DNA-binding protein and is localized in all cell nuclei through development as revealed by a GFP reporter construct. Disruption of son-1 function by RNA-mediated interference results in the same spicule defect as caused by overexpression of POP-1, a TCF/LEF class HMG protein known to act downstream of the Wnt signaling pathway. Our results provide in vivo evidence for the functional involvement of an HMG1/2-like protein, SON-1, in Wnt signaling. The sequence nonspecific HMG protein SON-1 and the sequence specific HMG protein POP-1 might both act in the Wnt responding cells to regulate gene transcription in opposite directions.
我们发现,在秀丽隐杆线虫雄性交合刺发育过程中,经典神经发生亚谱系中神经胶质细胞与神经元细胞命运的特化取决于Wnt信号通路。由Wnt受体LIN-17介导的Wnt信号通路失活会将SPD鞘细胞转变为其姐妹细胞,即SPD神经元。我们发现了一个新的突变体son-1,它表现出相同的细胞命运转变。son-1突变在包括阴门发育、体细胞性腺发育和雄性尾部模式形成在内的几个发育过程中增强了功能缺失型lin-17突变体的表型。son-1编码一种HMG1/2样DNA结合蛋白,并且如绿色荧光蛋白报告基因构建体所显示的那样,在整个发育过程中定位于所有细胞核中。通过RNA介导的干扰破坏son-1功能会导致与已知在Wnt信号通路下游起作用的TCF/LEF类HMG蛋白POP-1过表达所引起的相同的交合刺缺陷。我们的结果为HMG1/2样蛋白SON-1在Wnt信号通路中的功能参与提供了体内证据。序列非特异性HMG蛋白SON-1和序列特异性HMG蛋白POP-1可能都在Wnt反应细胞中起作用,以相反的方向调节基因转录。