ztf-16 is a novel heterochronic modulator that opposes adult cell fate in dauer and continuous life histories in Caenorhabditis elegans

Hansen, M. A.; Dahal, A.; Bernstein, T. A.; Kohtz, C.; Ali, S.; Daul, A. L.; Montoye, E. A.; Panzade, G. P.; Alessi, A. F.; Flibotte, S.; Vargas, M. L.; Bourgeois, J.; Brown, C. J.; Kim, J. K.; Rougvie, A. E.; Zinovyeva, A.; Karp, X.

doi:10.1101/2022.06.20.496913

bioRxiv · 10.1101/2022.06.20.496913

ztf-16 is a novel heterochronic modulator that opposes adult cell fate in dauer and continuous life histories in Caenorhabditis elegans

Hansen, M. A.·Dahal, A.·Bernstein, T. A.·Kohtz, C.·Ali, S.·Daul, A. L.·Montoye, E. A.·Panzade, G. P.·Alessi, A. F.·Flibotte, S.·Vargas, M. L.·Bourgeois, J.·Brown, C. J.·Kim, J. K.·Rougvie, A. E.·Zinovyeva, A.·Karp, X.

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Abstract

Animal development is a complex yet robust process that can withstand lengthy and variable interruptions. In Caenorhabditis elegans, adverse conditions can trigger entry into dauer diapause, a stress-resistant, developmentally arrested stage that occurs midway through larval development. Favorable conditions promote recovery from dauer and the completion of development. During larval development, hypodermal seam cells are multipotent and divide at each stage. At adulthood, seam cells differentiate and express the adult-specific COL-19 collagen. The larval-to-adult transition is controlled by a network of genes called the heterochronic pathway, including the LIN-29 transcription factor that directly activates col-19 expression, and the let-7 microRNA that indirectly promotes lin-29 expression. Notably, most heterochronic genes that oppose adult cell fate are dispensable after dauer. We performed a genetic screen for heterochronic genes that act after dauer and identified ztf-16, encoding a zinc finger transcription factor in the hunchback/Ikaros-like family. We found that ztf-16 opposes precocious expression of the adult cell fate marker col-19p::gfp equally during both life histories, making ztf-16(-) the first precocious heterochronic mutant to be unaffected by dauer. Our data indicate that ztf-16 regulates col-19p::gfp via a novel, lin-29-independent mechanism. Endogenous ztf-16b::gfp expression is regulated by let-7 and ztf-16 acts genetically downstream of let-7, but lin-29 is not required for col-19p::gfp expression in ztf-16 mutant larvae or adults. Taken together, this work illuminates a novel aspect of the heterochronic pathway relevant to both dauer and non-dauer development.

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Hansen, M. A., Dahal, A., Bernstein, T. A., Kohtz, C., Ali, S., Daul, A. L., Montoye, E. A., Panzade, G. P., Alessi, A. F., Flibotte, S., Vargas, M. L., Bourgeois, J., Brown, C. J., Kim, J. K., Rougvie, A. E., Zinovyeva, A., Karp, X.. 2022-06-22. ztf-16 is a novel heterochronic modulator that opposes adult cell fate in dauer and continuous life histories in Caenorhabditis elegans. https://doi.org/10.1101/2022.06.20.496913

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