title: Nutrient-Dependent Endocycling in Steroidogenic Tissue Dictates Timing of Metamorphosis in Drosophila melanogaster.
abstract: Many animals have an intrinsic growth checkpoint during juvenile development, after which an irreversible decision is made to upregulate steroidogenesis, triggering the metamorphic juvenile-to-adult transition. However, a molecular process underlying such a critical developmental decision remains obscure. Here we show that nutrient-dependent endocycling in steroidogenic cells provides the machinery necessary for irreversible activation of metamorphosis in Drosophila melanogaster. Endocycle progression in cells of the prothoracic gland (PG) is tightly coupled with the growth checkpoint, and block of endocycle in PG cells causes larval developmental arrest due to reduction in biosynthesis of the steroid hormone ecdysone. Moreover, inhibition of the nutrient sensor target of rapamycin (TOR) in the PG during the checkpoint period causes endocycle inhibition and developmental arrest, which can be rescued by inducing additional rounds of endocycles by Cyclin E. We propose that a TOR-mediated cell cycle checkpoint in steroidogenic tissue provides a systemic growth checkpoint for reproductive maturation.
authors.affiliation: Department of Entomology, Institute for Integrative Genome Biology, Center for Disease Vector Research, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ohhara
authors.affiliation: Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Entomology, Institute for Integrative Genome Biology, Center for Disease Vector Research, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Naoki
authors.identifier: 0000-0002-6244-2686
authors.initials: N
authors.lastname: Yamanaka
mesh_terms: D000818:Animals; D002453:Cell Cycle; D019927:Cyclin E / Q000378:metabolism; D004261:DNA Replication; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D004440:Ecdysone / Q000096:biosynthesis* / Q000235:genetics; D055098:Endocrine Cells / Q000378:metabolism; D005502:Food; D008675:Metamorphosis, Biological; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D019927:Cyclin E; D004440:Ecdysone; D058570:TOR Serine-Threonine Kinases