| Title: | Pheromones and Nutritional Signals Regulate the Developmental Reliance on let-7 Family MicroRNAs in C. elegans |
| Address: | "Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA. Electronic address: victor.ambros@umassmed.edu" |
| DOI: | 10.1016/j.cub.2019.04.034 |
| ISSN/ISBN: | 1879-0445 (Electronic) 0960-9822 (Print) 0960-9822 (Linking) |
| Abstract: | "Adverse environmental conditions can affect rates of animal developmental progression and lead to temporary developmental quiescence (diapause), exemplified by the dauer larva stage of the nematode Caenorhabditis elegans (C. elegans). Remarkably, patterns of cell division and temporal cell-fate progression in C. elegans larvae are not affected by changes in developmental trajectory. However, the underlying physiological and gene regulatory mechanisms that ensure robust developmental patterning despite substantial plasticity in developmental progression are largely unknown. Here, we report that diapause-inducing pheromones correct heterochronic developmental cell lineage defects caused by insufficient expression of let-7 family microRNAs in C. elegans. Moreover, two conserved endocrine signaling pathways, DAF-7/TGF-beta and DAF-2/Insulin, that confer on the larva diapause and non-diapause alternative developmental trajectories interact with the nuclear hormone receptor, DAF-12, to initiate and regulate a rewiring of the genetic circuitry controlling temporal cell fates. This rewiring includes engagement of certain heterochronic genes, lin-46, lin-4, and nhl-2, that are previously associated with an altered genetic program in post-diapause animals, in combination with a novel ligand-independent DAF-12 activity, to downregulate the critical let-7 family target Hunchback-like-1 (HBL-1). Our results show how pheromone or endocrine signaling pathways can coordinately regulate both developmental progression and cell-fate transitions in C. elegans larvae under stress so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory" |
| Keywords: | Animals Caenorhabditis elegans/genetics/growth & development/*physiology Cell Lineage/genetics Diapause/*genetics Larva/genetics/growth & development/physiology MicroRNAs/*genetics/metabolism Pheromones/*metabolism *Signal Transduction ascarosides dauer l; |
| Notes: | "MedlineIlbay, Orkan Ambros, Victor eng P40 OD010440/OD/NIH HHS/ R01 GM034028/GM/NIGMS NIH HHS/ R01 GM088365/GM/NIGMS NIH HHS/ R35 GM131741/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural England 2019/05/21 Curr Biol. 2019 Jun 3; 29(11):1735-1745.e4. doi: 10.1016/j.cub.2019.04.034. Epub 2019 May 16" |
