daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71

Matthew J Wirick ¹, Allison R Cale ^2,3, Isaac T Smith ²

⁰Biochemistry, Cell & Molecular Biology Program, Central Michigan University, Mt Pleasant, Michigan, United States of America.

Plos Genetics +

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November 15, 2021

View abstract on PubMed

Summary

The FOXO transcription factor DAF-16 maintains stem cell multipotency during C. elegans dauer quiescence by upregulating the heterochronic gene LIN-41. This prevents premature differentiation and ensures proper development resumption.

Area Of Science

Developmental Biology
Stem Cell Biology
Genetics

Background

Tissue-specific stem cells can remain multipotent during quiescence.
FOXO transcription factors, like DAF-16 in C. elegans, are known to promote quiescence and stem cell maintenance.
The precise mechanisms by which FOXO proteins maintain multipotency during quiescence are still being elucidated.

Purpose Of The Study

To investigate the role of DAF-16/FOXO in maintaining stem cell multipotency during the quiescent dauer larval stage in C. elegans.
To identify the molecular pathways regulated by DAF-16 during dauer that control cell fate decisions.
To understand how DAF-16 interacts with the heterochronic gene network to regulate developmental timing.

Main Methods

Utilized C. elegans as a model organism.
Employed a col-19p::gfp reporter to mark adult epidermal cell fate.
Assessed gene expression and protein function through genetic mutations (daf-16(0)) and isoform analysis.
Investigated the roles of heterochronic genes lin-41 and lin-29 in DAF-16-mediated regulation.

Main Results

DAF-16/FOXO prevents epidermal stem cells (seam cells) from adopting adult characteristics during dauer.
Loss of DAF-16 in dauer larvae leads to misexpression of adult-enriched collagens (col-19p::gfp).
DAF-16 promotes the expression of the heterochronic gene lin-41 during dauer, which is crucial for suppressing adult cell fate.
LIN-41 acts downstream of DAF-16 to inhibit premature adult cell fate, independent of LIN-29 in the dauer context.

Conclusions

DAF-16/FOXO functions as a heterochronic gene to maintain stem cell multipotency during quiescence.
DAF-16 promotes the expression of lin-41/TRIM71, a key regulator of developmental timing.
This study reveals a novel mechanism by which FOXO transcription factors ensure stem cell preparedness for future development after periods of stress or quiescence.