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

Development. 2022 Nov 1;149(21):dev201094. 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.

Keywords: C. elegans; Dauer; EGFR; ERK; Ras; Vulva.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins* / metabolism
  • Diapause*
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Signal Transduction / genetics
  • Vulva

Substances

  • Caenorhabditis elegans Proteins
  • Epidermal Growth Factor
  • ErbB Receptors