title: Ecdysone signaling induces two phases of cell cycle exit in Drosophila cells.
abstract: During development, cell proliferation and differentiation must be tightly coordinated to ensure proper tissue morphogenesis. Because steroid hormones are central regulators of developmental timing, understanding the links between steroid hormone signaling and cell proliferation is crucial to understanding the molecular basis of morphogenesis. Here we examined the mechanism by which the steroid hormone ecdysone regulates the cell cycle in Drosophila We find that a cell cycle arrest induced by ecdysone in Drosophila cell culture is analogous to a G2 cell cycle arrest observed in the early pupa wing. We show that in the wing, ecdysone signaling at the larva-to-puparium transition induces Broad which in turn represses the cdc25c phosphatase String. The repression of String generates a temporary G2 arrest that synchronizes the cell cycle in the wing epithelium during early pupa wing elongation and flattening. As ecdysone levels decline after the larva-to-puparium pulse during early metamorphosis, Broad expression plummets, allowing String to become re-activated, which promotes rapid G2/M progression and a subsequent synchronized final cell cycle in the wing. In this manner, pulses of ecdysone can both synchronize the final cell cycle and promote the coordinated acquisition of terminal differentiation characteristics in the wing.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Flegel
authors.affiliation: Biology Department and Genetics Department, Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Kumar
authors.affiliation: Biology Department and Genetics Department, Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McKay
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA buttitta@umich.edu.
authors.forename: Laura A
authors.identifier: http://orcid.org/0000-0002-5064-0650
authors.initials: LA
authors.lastname: Buttitta
keywords: Cell cycle; Drosophila; Ecdysone; Metamorphosis; Steroid hormone