Paired box (Pax) proteins function as regulators of coordinated development in organogenesis by controlling factors such as cell growth and differentiation necessary to organize multiple cell types into a single, cohesive organ. Previous work has suggested that Pax transcription factors may regulate diverse cell types through participation in inductive cell-to-cell signaling, which has not been well explored. Here we show that EGL-38, a Pax2/5/8 ortholog, coordinates differentiation of the C. elegans egg-laying system through separate autonomous and non-autonomous functions synchronized by the EGF pathway. We find that EGL-38 protein is expressed at the correct times to both participate in and respond to the EGF pathway specifying uterine ventral (uv1) cell fate, and that EGL-38 is required for uv1 expression of nlp-2 and nlp-7, which are both markers of and participants in uv1 identity. Additionally, we have separated uv1 cell placement and gene expression as distinct hallmarks of uv1 identity and specification, with different dependencies on EGL-38. The parallels between EGL-38 participation in cell signaling events and previous Pax studies argue that coordination of signaling and response to an inductive pathway may be a common feature of Pax protein function.

中文翻译：

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EGL-38/Pax 通过 EGF 通路依赖和独立的功能协调秀丽隐杆线虫产卵系统的发育

配对盒 (Pax) 蛋白通过控制细胞生长和分化等因素将多种细胞类型组织成一个单一的、有凝聚力的器官，从而起到器官发生协调发展的调节作用。先前的工作表明，Pax 转录因子可以通过参与诱导性细胞间信号传导来调节多种细胞类型，但尚未得到充分探索。在这里，我们展示了 EGL-38，一种 Pax2/5/8 直向同源物，通过由 EGF 途径同步的独立自主和非自主功能协调线虫产卵系统的分化。我们发现 EGL-38 蛋白在正确的时间表达以参与和响应指定子宫腹侧 (uv1) 细胞命运的 EGF 途径，并且 EGL-38 是 nlp-2 和 nlp-7 的 uv1 表达所必需的, 它们既是 uv1 身份的标记又是参与者。此外，我们将 uv1 细胞放置和基因表达作为 uv1 身份和规格的不同标志分开，对 EGL-38 具有不同的依赖性。EGL-38 参与细胞信号事件与之前的 Pax 研究之间的相似之处表明，信号传导和对诱导途径的反应的协调可能是 Pax 蛋白功能的一个共同特征。