Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Development. 2013 May;140(10):2093-102. doi: 10.1242/dev.091124.
The C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development.
秀丽隐杆线虫的体节细胞是从前端到后端排列成单行的侧上皮细胞,在幼虫发育过程中以不对称的、类似于干细胞的方式分裂。这些不对称分裂受 Wnt 信号调控;在大多数分裂中,激活 Wnt 途径的后裔女儿保持祖细胞体节命运,而未激活 Wnt 途径的前裔女儿则采用分化的真皮命运。通过 mRNA 标记和微阵列分析,我们确定了功能冗余的 GATA 因子基因 egl-18 和 elt-6 是幼虫体节细胞中 Wnt 途径的靶基因。EGL-18 和 ELT-6 先前已被证明是胚胎中初始体节细胞特化所必需的。我们表明,在幼虫体节细胞不对称分裂中,EGL-18 在后部体节命运的女儿中强烈表达。egl-18 和 elt-6 对于幼虫体节细胞的特化以及由异位 Wnt 途径过度激活诱导的真皮到体节细胞命运转变是必需的。TCF 同源物 POP-1 在体外结合 egl-18 启动子中的一个位点,该位点对于体内体节细胞的强表达是必需的。最后,幼虫过表达 EGL-18 足以在野生型动物中的其他真皮细胞中驱动体节标记的表达,并在 Wnt 信号敏感背景中的前真皮命运的女儿中驱动表达。这些数据表明,两个在胚胎中独立于 Wnt 信号对体节细胞特化所必需的 GATA 因子在 Wnt 信号下游被重新用于在幼虫发育中维持类似于干细胞的分裂中的祖细胞命运。