RRC ID 3541
Author Ruaud AF, Bessereau JL.
Title Activation of nicotinic receptors uncouples a developmental timer from the molting timer in C. elegans.
Journal Development
Abstract C. elegans develops through four larval stages (L1 to L4) separated by molts. The identity of larval stages is mostly determined by stage-specific expression of heterochronic genes, which constitute an intrinsic genetic timer. However, extrinsic cues such as food availability or population density also modulate the developmental timing of C. elegans by mechanisms that remain largely unknown. To investigate a potential role of the nervous system in the temporal regulation of C. elegans development, we pharmacologically manipulated nicotinic neurotransmission, which represents a prominent signaling component in C. elegans nervous system. Exposure to the nicotinic agonist DMPP during post-embryonic development is lethal at the L2/L3 molt. Specifically, it delays cell divisions and differentiation during the L2 stage but does not affect the timing of the molt cycle, hence causing exposure of a defective L3 cuticle to the environment after the L2/L3 molt. Forcing development through a previously uncharacterized L2 diapause resynchronizes these events and suppresses DMPP-induced lethality. Nicotinic acetylcholine receptors (nAChRs) containing the UNC-63 subunit are required, probably in neurons, to trigger the action of DMPP. Using a forward genetic screen, we further demonstrated that the nuclear hormone receptor (NHR) DAF-12 is necessary to implement the developmental effects of DMPP. Therefore, a novel neuroendocrine pathway involving nAChRs and the NHR DAF-12 can control the speed of stage-specific developmental events in C. elegans. Activation of DMPP-sensitive nAChRs during the second larval stage uncouples a molting timer and a developmental timer, thus causing a heterochronic phenotype that is lethal at the subsequent molt.
Volume 133(11)
Pages 2211-22
Published 2006-6
DOI 10.1242/dev.02392
PII dev.02392
PMID 16672334
MeSH Animals Biological Clocks / physiology* Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism Dimethylphenylpiperazinium Iodide / toxicity Gene Expression Regulation, Developmental Microscopy, Electron Molting / physiology* Mutation / genetics Protein Binding Protein Subunits / genetics Protein Subunits / metabolism Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism Receptors, Nicotinic / genetics Receptors, Nicotinic / metabolism* Time Factors
IF 5.763
Times Cited 43
C.elegans tm863