title: The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition.
abstract: Developmental timing in the nematode Caenorhabditis elegans is controlled by heterochronic genes, mutations in which cause changes in the relative timing of developmental events. One of the heterochronic genes, let-7, encodes a microRNA that is highly evolutionarily conserved, suggesting that similar genetic pathways control developmental timing across phyla. Here we report that the nuclear receptor nhr-25, which belongs to the evolutionarily conserved fushi tarazu-factor 1/nuclear receptor NR5A subfamily, interacts with heterochronic genes that regulate the larva-to-adult transition in C. elegans. We identified nhr-25 as a regulator of apl-1, a homolog of the Alzheimer's amyloid precursor protein-like gene that is downstream of let-7 family microRNAs. NHR-25 controls not only apl-1 expression but also regulates developmental progression in the larva-to-adult transition. NHR-25 negatively regulates the expression of the adult-specific collagen gene col-19 in lateral epidermal seam cells. In contrast, NHR-25 positively regulates the larva-to-adult transition for other timed events in seam cells, such as cell fusion, cell division and alae formation. The genetic relationships between nhr-25 and other heterochronic genes are strikingly varied among several adult developmental events. We propose that nhr-25 has multiple roles in both promoting and inhibiting the C. elegans heterochronic gene pathway controlling adult differentiation programs.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hada
authors.forename: Masako
authors.initials: M
authors.lastname: Asahina
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Slack
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Niwa
mesh_terms: D000818:Animals; D002107:Caenorhabditis / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D053263:Gene Regulatory Networks; D007814:Larva / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear