Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Development. 2022 Nov 1;149(21). doi: 10.1242/dev.201094. Epub 2022 Oct 31.
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.
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。