Laboratory of Developmental Genetics, The Rockefeller University, New York, New York 10065, USA.
Genetics. 2012 Apr;190(4):1405-15. doi: 10.1534/genetics.111.137786. Epub 2012 Jan 31.
Neurons and glia display remarkable morphological plasticity, and remodeling of glia may facilitate neuronal shape changes. The molecular basis and control of glial shape changes is not well understood. In response to environmental stress, the nematode Caenorhabditis elegans enters an alternative developmental state, called dauer, in which glia and neurons of the amphid sensory organ remodel. Here, we describe a genetic screen aimed at identifying genes required for amphid glia remodeling. We previously demonstrated that remodeling requires the Otx-type transcription factor TTX-1 and its direct target, the receptor tyrosine kinase gene ver-1. We now find that the hunchback/Ikaros-like C2H2 zinc-finger factor ztf-16 is also required. We show that ztf-16 mutants exhibit pronounced remodeling defects, which are explained, at least in part, by defects in the expression of ver-1. Expression and cell-specific rescue studies suggest that ztf-16, like ttx-1, functions within glia; however, promoter deletion studies show that ztf-16 acts through a site on the ver-1 promoter that is independent of ttx-1. Our studies identify an important component of glia remodeling and suggest that transcriptional changes may underlie glial morphological plasticity in the sensory organs of C. elegans.
神经元和神经胶质显示出显著的形态可塑性，神经胶质的重塑可能有助于神经元形态的变化。神经胶质形态变化的分子基础和调控机制还不太清楚。在应对环境压力时，秀丽隐杆线虫进入一种称为 dauer 的替代发育状态，在此状态下，触角感觉器官的神经胶质和神经元会发生重塑。在这里，我们描述了一项旨在鉴定参与触角神经胶质重塑所需基因的遗传筛选。我们之前证明，重塑需要 Otx 型转录因子 TTX-1 及其直接靶标、受体酪氨酸激酶基因 ver-1。我们现在发现 hunchback/Ikaros 样 C2H2 锌指因子 ztf-16 也同样需要。我们表明，ztf-16 突变体表现出明显的重塑缺陷，这至少部分归因于 ver-1 表达的缺陷。表达和细胞特异性拯救研究表明，ztf-16 与 ttx-1 一样，在神经胶质中发挥作用；然而，启动子缺失研究表明，ztf-16 通过独立于 ttx-1 的 ver-1 启动子上的一个位点发挥作用。我们的研究确定了神经胶质重塑的一个重要组成部分，并表明转录变化可能是秀丽隐杆线虫感觉器官神经胶质形态可塑性的基础。
