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在 dauer 休眠期间,秀丽隐杆线虫的表皮前体细胞中 EGFR 信号转导被下调。

EGFR signal transduction is downregulated in C. elegans vulval precursor cells during dauer diapause.

机构信息

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

出版信息

Development. 2022 Nov 1;149(21). doi: 10.1242/dev.201094. Epub 2022 Oct 31.

Abstract

Caenorhabditis elegans larvae display developmental plasticity in response to environmental conditions: in adverse conditions, second-stage larvae enter a reversible, long-lived dauer stage instead of proceeding to reproductive adulthood. Dauer entry interrupts vulval induction and is associated with a reprogramming-like event that preserves the multipotency of vulval precursor cells (VPCs), allowing vulval development to reinitiate if conditions improve. Vulval induction requires the LIN-3/EGF-like signal from the gonad, which activates EGFR-Ras-ERK signal transduction in the nearest VPC, P6.p. Here, using a biosensor and live imaging we show that EGFR-Ras-ERK activity is downregulated in P6.p in dauers. We investigated this process using gene mutations or transgenes to manipulate different steps of the pathway, and by analyzing LET-23/EGFR subcellular localization during dauer life history. We found that the response to EGF is attenuated at or upstream of Ras activation, and discuss potential membrane-associated mechanisms that could achieve this. We also describe other findings pertaining to the maintenance of VPC competence and quiescence in dauer larvae. Our analysis indicates that VPCs have L2-like and unique dauer stage features rather than features of L3 VPCs in continuous development.

摘要

秀丽隐杆线虫幼虫在环境条件下表现出发育可塑性

在不利条件下,第二阶段幼虫进入可逆的、长寿的 dauer 阶段,而不是进入生殖成年期。 dauer 进入会中断阴道诱导,并与类似于重编程的事件相关联,该事件保留了阴道前体细胞(VPC)的多能性,允许在条件改善时重新启动阴道发育。阴道诱导需要来自性腺的 LIN-3/EGF 样信号,该信号在最近的 VPC P6.p 中激活 EGFR-Ras-ERK 信号转导。在这里,我们使用生物传感器和活体成像显示,在 dauer 中 P6.p 中的 EGFR-Ras-ERK 活性下调。我们使用基因突变或转基因来操纵该途径的不同步骤,以及通过分析 LET-23/EGFR 亚细胞定位在 dauer 生命史期间来研究这个过程。我们发现,EGF 反应在 Ras 激活或其上游减弱,并且讨论了可以实现这一点的潜在膜相关机制。我们还描述了与 dauer 幼虫中 VPC 能力和静止的维持有关的其他发现。我们的分析表明,VPC 具有 L2 样和独特的 dauer 阶段特征,而不是连续发育中 L3 VPC 的特征。

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