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

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, a stress-resistant, developmentally arrested diapause stage that occurs midway through larval development. Favorable conditions promote recovery from dauer, and post-dauer larvae develop normally. During larval development, epidermal seam cells are multipotent and divide at each stage. At adulthood, seam cells differentiate and express the adult-specific COL-19 collagen. The progression of cell fates 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 known heterochronic genes that oppose adult cell fate act only during continuous development; these genes 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 is required to prevent 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. Finally, mRNA-seq experiments identified genes whose expression is regulated by ztf-16 in each life history. Taken together, this work illuminates a novel aspect of the heterochronic pathway relevant to both dauer and non-dauer development.