RRC ID 45708
Author Chen Y, Baugh LR.
Title Ins-4 and daf-28 function redundantly to regulate C. elegans L1 arrest.
Journal Dev Biol
Abstract Caenorhabditis elegans larvae reversibly arrest development in the first larval stage in response to starvation (L1 arrest or L1 diapause). Insulin-like signaling is a critical regulator of L1 arrest. However, the C. elegans genome encodes 40 insulin-like peptides, and it is unknown which peptides participate in nutritional control of L1 development. Work in other contexts has revealed that insulin-like genes can promote development ("agonists") or developmental arrest ("antagonists"), suggesting that such agonists promote L1 development in response to feeding. We measured mRNA expression dynamics with high temporal resolution for all 40 insulin-like genes during entry into and recovery from L1 arrest. Nutrient availability influences expression of the majority of insulin-like genes, with variable dynamics suggesting complex regulation. We identified thirteen candidate agonists and eight candidate antagonists based on expression in response to nutrient availability. We selected ten candidate agonists (daf-28, ins-3, ins-4, ins-5, ins-6, ins-7, ins-9, ins-26, ins-33 and ins-35) for further characterization in L1 stage larvae. We used destabilized reporter genes to determine spatial expression patterns. Expression of candidate agonists is largely overlapping in L1 stage larvae, suggesting a role of the intestine, chemosensory neurons ASI and ASJ, and the interneuron PVT in control of L1 development. Transcriptional regulation of candidate agonists is most significant in the intestine, as if internal nutrient status is a more important influence on transcription than sensory perception. Phenotypic analysis of single and compound deletion mutants did not reveal effects on L1 developmental dynamics, though simultaneous disruption of ins-4 and daf-28 increases survival of L1 arrest. Furthermore, overexpression of ins-4, ins-6 or daf-28 alone decreases survival and promotes cell division during starvation. These results suggest extensive functional overlap among insulin-like genes in nutritional control of L1 development while highlighting the role of ins-4, daf-28 and to a lesser extent ins-6.
Volume 394(2)
Pages 314-26
Published 2014-10-15
DOI 10.1016/j.ydbio.2014.08.002
PII S0012-1606(14)00378-9
PMID 25128585
MeSH Analysis of Variance Animals Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Expression Profiling Gene Expression Regulation, Developmental / physiology* Insulin / agonists Insulin / metabolism Insulins Intestinal Mucosa / metabolism Larva / growth & development Larva / metabolism Logistic Models Peptide Hormones / genetics Peptide Hormones / metabolism* RNA, Messenger / metabolism* Receptor, Insulin / metabolism* Survival Analysis
IF 2.896
Times Cited 24
C.elegans tm2308 tm3620 tm2560 tm2416 tm2001 tm3618 tm1983 tm2988