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

Area of Science:

• Developmental Biology
• Neurobiology
• Cell Biology

Background:

• Cell migration is crucial for embryonic development and disease, with acetylcholine (ACh) signaling implicated in various cell movements.
• In vivo studies on the role of nicotinic ACh receptors (nAChRs) in cell migration are limited.
• The linker cell (LC) in C. elegans gonadogenesis provides a model to study directed cell migration.

Purpose of the Study:

• To investigate the in vivo function of nAChRs in the migration of the C. elegans linker cell (LC).
• To elucidate the role of acetylcholine (ACh) signaling in regulating LC polarity and migration.
• To identify the specific nAChR subunits and cell adhesion molecules involved in LC directional changes.

Main Methods:

• Utilized Caenorhabditis elegans (C. elegans) male gonadogenesis as a model system.
• Manipulated acetylcholine (ACh) levels to observe effects on LC migration and polarity.
• Employed genetic analysis of nAChR mutants (acr-16, lgc-9, acr-15) and L1 cell adhesion molecule (SAX-7) mutants.

Main Results:

• Excess ACh induced a reorientation of LC polarity from posterior to ventral facing, requiring nAChRs.
• Specific nAChR subunits differentially affected LC reversal: acr-16(-) and lgc-9(-) inhibited, while acr-15(-) promoted reversals.
• LC reversal in response to excess ACh depended on the L1 cell adhesion molecule SAX-7, expressed in both the ventral nerve cord (VNC) and LC.

Conclusions:

• ACh signaling through specific nAChRs regulates LC migration direction during C. elegans gonadogenesis.
• SAX-7 mediated adhesion is critical for ACh-induced LC reorientation.
• This study provides in vivo evidence for nAChR function in directed cell migration and proposes a mechanism involving adhesion modulation.