Most adult stem cells are multipotent and found in a state of reversible cell cycle arrest known as quiescence. However, the mechanisms that maintain multipotency during quiescence are relatively unknown. We use C. elegans as a model organism to study this process. C. elegans larvae develop through one of two different life histories: continuous or dauer. Dauer is a stress-resistant and developmentally arrested stage occurring after the second larval molt in response to adverse environmental conditions. If conditions improve, dauer larvae recover and complete development normally. C. elegans contains a set of stem cell-like seam cells that undergo specific division patterns at each larval stage, resulting in self-renewal and generation of
hyp7 nuclei. During dauer, seam cells remain multipotent and quiescent, modeling mammalian stem cells. Following recovery from dauer, seam cells complete their development identically to larvae that did not experience dauer. Heterochronic genes ensure correct temporal control of seam cell division and differentiation. At adulthood, seam cells terminally differentiate, which can be visualized by the expression of the adult cell fate marker
col-19::gfp. Intriguingly, many heterochronic genes that are required during continuous development are dispensable after dauer, suggesting that there is a separate genetic pathway operating during this time. To identify heterochronic genes that function after dauer, we performed a genetic screen for mutants with precocious post-dauer
col-19::gfp expression. We screened 6000 genomes and isolated five independent alleles with high penetrance phenotypes. Using whole-genome sequencing, we found that two alleles contain mutations in
ztf-16, which encodes a zinc finger transcription factor. We are currently confirming that
ztf-16 is the causal mutation by rescue experiments and looking for phenocopy with RNAi and established
ztf-16 mutations. Using established alleles plus our newly identified mutations, we find that
ztf-16 is required to prevent precocious
col-19::gfp expression during both continuous and dauer development. Furthermore, passage through dauer does not correct the
ztf-16 precocious phenotype, making it unique among characterized precocious mutants. Ongoing genetic experiments are investigating the position of
ztf-16 within the heterochronic pathway and determining its relevant expression pattern. Characterization of
ztf-16 will shed light on mechanisms that maintain multipotency throughout quiescence.