Poster abstracts
Poster number 159 submitted by Matthew Wirick
FOXO/daf-16 opposes the expression of the conserved let-7 microRNA to regulate epidermal seam cell multipotency in C. elegans
Matthew J. Wirick (Department of Biology, Central Michigan University), Himani Galagali (Department of Biology, Johns Hopkins University), Amelia F. Alessi (Department of Biology, Johns Hopkins University), Allison R. Cale (Department of Biology, Central Michigan University), John K. Kim (Department of Biology, Johns Hopkins University), Xantha Karp (Department of Biology, Central Michigan University)
Abstract:
Tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote stem cell maintenance and quiescence. Conversely, expression of the conserved let-7 microRNA promotes differentiation in stem cell models. However, the interaction between these two factors has not been defined. In response to adverse environmental conditions, C. elegans larvae can enter a developmentally arrested stage called dauer, where progenitor cells are quiescent and maintain multipotency until development resumes. Here, we examine the role of the FOXO ortholog, daf-16, and let-7 in the fate of multipotent seam cells during dauer. We found that daf-16(0) dauer larvae expressed a seam cell differentiation marker, col-19p::gfp, indicating that daf-16 promotes multipotency in seam cells. During non-dauer development, let-7 functions to promote differentiation and col-19p::gfp expression in seam cells. We found that daf-16 regulates seam cell differentiation at least partially though microRNAs because loss of a microRNA-specific Argonaute suppressed the expression of col-19p::gfp in daf-16(0) dauer larvae. Furthermore, daf-16(0) dauer larvae displayed increased levels of let-7. This increase in let-7 expression is functionally relevant because daf-16(0) dauer larvae display reduced col-19p::gfp expression when let-7 activity is reduced or when the let-7 binding sites are removed from a let-7 target, lin-41. Using a let-7 transcriptional reporter and mutations within the let-7 promoter, we found that daf-16 indirectly promotes the transcription of let-7 before dauer. Taken together, this work demonstrates the first instance of FOXO/daf-16 proteins regulating cell fate decisions via let-7, which provides a framework for an interaction of these two genes in mammalian stem cells.
Keywords: C elegans, FOXO, let-7