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.
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Related Subject Headings
- Transcription Factors
- Somatomedins
- Repressor Proteins
- Nutritional Requirements
- MicroRNAs
- Gene Expression Regulation, Developmental
- Forkhead Transcription Factors
- Developmental Biology
- Cyclin-Dependent Kinase Inhibitor Proteins
- Caenorhabditis elegans Proteins
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Transcription Factors
- Somatomedins
- Repressor Proteins
- Nutritional Requirements
- MicroRNAs
- Gene Expression Regulation, Developmental
- Forkhead Transcription Factors
- Developmental Biology
- Cyclin-Dependent Kinase Inhibitor Proteins
- Caenorhabditis elegans Proteins