Nicotinic acetylcholine receptors function with adhesion molecule SAX-7 to reverse cell orientation during migration

Abstract

Cell migration is an important process underlying animal embryonic body patterning, organogenesis, and diseases like metastatic cancer. Acetylcholine (ACh) signaling plays a key role in the migration of various cell types and cancer cells, yet in vivo studies are lacking. We investigated the function of nicotinic ACh receptors (nAChRs) on the migration of a gonadal leader cell, the linker cell (LC). During C. elegans male gonadogenesis, the LC migrates posteriorly along the ventral body wall, following a path that runs parallel and adjacent to the ACh-releasing ventral nerve cord (VNC). Excess ACh reoriented the polarity of the LC from posterior-facing to anterior-facing through an intermediate stage of facing the ventral body wall. nAChRs, which are expressed by both the VNC and LC, were required for the LC reversal response. The specific combination of subunits of the pentameric nAChR produced different reversal responses, with acr-16(-) and lgc-9(-) mutants inhibiting and acr-15(-) promoting reversals. LC reversal in response to excess ACh also required the L1 cell adhesion molecule (L1CAM), SAX-7, which is expressed by both VNC and LC. We propose that an increase in ACh signaling in the VNC and LC promotes stronger SAX-7 mediated adhesion of the LC to the ventral body wall, causing the LC to change directions from posterior to ventral facing.

Keywords: C. elegans gonadogenesis; Cell migration; L1CAM; Nicotinic acetylcholine receptor.