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dc.contributor.authorIlbay, Orkan
dc.contributor.authorAmbros, Victor R.
dc.date2022-08-11T08:10:18.000
dc.date.accessioned2022-08-23T17:03:48Z
dc.date.available2022-08-23T17:03:48Z
dc.date.issued2019-06-03
dc.date.submitted2019-07-08
dc.identifier.citation<p>Curr Biol. 2019 Jun 3;29(11):1735-1745.e4. doi: 10.1016/j.cub.2019.04.034. Epub 2019 May 16. <a href="https://doi.org/10.1016/j.cub.2019.04.034">Link to article on publisher's site</a></p>
dc.identifier.issn0960-9822 (Linking)
dc.identifier.doi10.1016/j.cub.2019.04.034
dc.identifier.pmid31104929
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44503
dc.description.abstractAdverse 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31104929&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.cub.2019.04.034
dc.subjectascarosides
dc.subjectdauer larva
dc.subjectdevelopmental robustness
dc.subjectendocrine signaling
dc.subjectheterochronic genes
dc.subjectlet-7
dc.subjectmicroRNAs
dc.subjectpheromones
dc.subjectreprogramming
dc.subjectstem cell
dc.subjectDevelopmental Biology
dc.titlePheromones and Nutritional Signals Regulate the Developmental Reliance on let-7 Family MicroRNAs in C. elegans
dc.typeJournal Article
dc.source.journaltitleCurrent biology : CB
dc.source.volume29
dc.source.issue11
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pmm_pp/99
dc.identifier.contextkey14880290
html.description.abstract<p>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.</p>
dc.identifier.submissionpathpmm_pp/99
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1735-1745.e4


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