DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest

Curr Biol. 2006 Apr 18;16(8):780-5. doi: 10.1016/j.cub.2006.03.021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology*
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism*
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental
  • MicroRNAs
  • Nutritional Requirements
  • Repressor Proteins / metabolism*
  • Somatomedins / physiology
  • Transcription Factors / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Forkhead Transcription Factors
  • MicroRNAs
  • Repressor Proteins
  • Somatomedins
  • Transcription Factors
  • cki-1 protein, C elegans
  • daf-16 protein, C elegans
  • lin-4 microRNA, C elegans