Howard Hughes Medical Institute, Division of Biology 156-29, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA.
Development. 2010 Jun;137(12):2065-74. doi: 10.1242/dev.040881.
The ancient origin of sleep is evidenced by deeply conserved signaling pathways regulating sleep-like behavior, such as signaling through the Epidermal growth factor receptor (EGFR). In Caenorhabditis elegans, a sleep-like state can be induced at any time during development or adulthood through conditional expression of LIN-3/EGF. The behavioral response to EGF is mediated by EGFR activity within a single cell, the ALA neuron, and mutations that impair ALA differentiation are expected to confer EGF-resistance. Here we describe three such EGF-resistant mutants. One of these corresponds to the LIM class homeodomain (HD) protein CEH-14/Lhx3, and the other two correspond to Paired-like HD proteins CEH-10/Chx10 and CEH-17/Phox2. Whereas CEH-14 is required for ALA-specific gene expression throughout development, the Prd-like proteins display complementary temporal contributions to gene expression, with the requirement for CEH-10 decreasing as that of CEH-17 increases. We present evidence that CEH-17 participates in a positive autoregulatory loop with CEH-14 in ALA, and that CEH-10, in addition to its role in ALA differentiation, functions in the generation of the ALA neuron. Similarly to CEH-17, CEH-10 is required for the posterior migration of the ALA axons, but CEH-14 appears to regulate an aspect of ALA axon outgrowth that is distinct from that of the Prd-like proteins. Our findings reveal partial modularity among the features of a neuronal differentiation program and their coordination by Prd and LIM class HD proteins.
睡眠的古老起源可以通过调节类似睡眠行为的信号通路来证明，例如通过表皮生长因子受体 (EGFR) 进行信号传递。在秀丽隐杆线虫中，通过 LIN-3/EGF 的条件表达，可以在发育或成年期的任何时间诱导类似睡眠的状态。EGF 的行为反应是由单个细胞内的 EGFR 活性介导的，这个细胞是 ALA 神经元，并且预计损害 ALA 分化的突变会导致对 EGF 的抗性。在这里，我们描述了三个这样的 EGF 抗性突变体。其中一个对应于 LIM 类同源结构域 (HD) 蛋白 CEH-14/Lhx3，另外两个对应于配对样 HD 蛋白 CEH-10/Chx10 和 CEH-17/Phox2。虽然 CEH-14 在整个发育过程中对于 ALA 特异性基因表达是必需的，但 Prd 样蛋白在基因表达方面表现出互补的时间贡献，随着 CEH-17 的需求增加，对 CEH-10 的需求减少。我们提供的证据表明，CEH-17 在 ALA 中与 CEH-14 参与正反馈回路，并且 CEH-10 除了在 ALA 分化中的作用外，还在 ALA 神经元的产生中发挥作用。与 CEH-17 类似，CEH-10 对于 ALA 轴突的后向迁移是必需的，但 CEH-14 似乎调节了与 Prd 样蛋白不同的 ALA 轴突生长方面。我们的发现揭示了神经元分化程序的特征及其由 Prd 和 LIM 类 HD 蛋白协调的部分模块化。
