DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest.
Development is typically studied as a continuous process under laboratory conditions, but wild animals often develop in variable and stressful environments. C. elegans larvae hatch in a developmentally arrested state (L1 arrest) and initiate post-embryonic development only in the presence of food (E. coli in lab). In contrast to the well-studied dauer arrest, L1 arrest occurs without morphological modification, although larvae in L1 arrest are more resistant to environmental stress than developing larvae . Consistent with its role in dauer formation and aging, we show that insulin/insulin-like growth factor (IGF) signaling regulates L1 arrest. daf-2 insulin/IGF receptor mutants have a constitutive-L1-arrest phenotype when fed and extended survival of L1 arrest when starved. Conversely, daf-16/FOXO mutants have a defective-arrest phenotype, failing to arrest development and dying rapidly when starved. We show that DAF-16 is required for transcription of the cyclin-dependent kinase inhibitor cki-1 in stem cells in response to starvation, accounting for the failure of daf-16/FOXO mutants to arrest cell division during L1 arrest. Other developmental events such as cell migration, cell fusion, and expression of the microRNA lin-4, a temporal regulator of post-embryonic development, are also observed in starved daf-16/FOXO mutants. These results suggest that DAF-16/FOXO promotes developmental arrest via transcriptional regulation of numerous target genes that control various aspects of development.
Baugh
L Ryan
LR
Howard Hughes Medical Institute and California Institute of Technology, Division of Biology, Pasadena, California 91125, USA.
Sternberg
Paul W
PW
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000502:physiology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs; D009751:Nutritional Requirements; D012097:Repressor Proteins / Q000378:metabolism*; D013002:Somatomedins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D012097:Repressor Proteins; D013002:Somatomedins; D014157:Transcription Factors; C115024:cki-1 protein, C elegans; C108831:daf-16 protein, C elegans; C452194:lin-4 microRNA, C elegans