| Dynamic control of cell cycle and growth coupling by ecdysone, EGFR, and PI3K signaling in Drosophila histoblasts. | |
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MedLine Citation:
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PMID: 19355788 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Regulation of cell proliferation has been extensively studied in cultured cell systems that are characterized by coordinated growth and cell-cycle progression and relatively uniform cell size distribution. During the development of multicellular organisms, however, growth and division can be temporally uncoupled, and the signaling pathways that regulate these growth programs are poorly understood. A good model for analyzing proliferation control in such systems is the morphogenesis of the Drosophila adult abdominal epidermis by histoblasts. These cells undergo a series of temporally regulated transitions during which neither cell size nor division rate is constant. The proliferation of histoblasts during metamorphosis is uniquely amenable to clonal analysis in combination with live imaging. Thereby, we show that abdominal histoblasts, which grow while in G2 arrest during larval stages, enter a proliferative stage in the pupal period that is initiated by ecdysone-dependent string/Cdc25 phosphatase transcription. The proliferating histoblasts have preaccumulated stores of Cyclin E, which trigger an immediate S phase onset after mitosis. These rapid cell cycles lack a G1 phase and result in a progressive reduction of cell size. Eventually, the histoblasts proceed to a stage of slower proliferation that, in contrast to the preceding, depends on epidermal growth factor receptor (EGFR) signaling for progression through the G2/M transition and on insulin receptor/PI3K-mediated signaling for growth. These results uncover the developmentally programmed changes coupling the growth and proliferation of the histoblasts that form the abdominal epidermis of Drosophila. Histoblasts proceed through three distinct stages: growth without division, division without growth, and growth-coupled proliferation. Our identification of the signaling pathways and cell-cycle regulators that control these programs illustrates the power of in vivo time-lapse analyses after clone induction. It sets the stage for the comprehensive understanding of the coordination of cell growth and cell-cycle progression in complex multicellular eukaryotes. |
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Authors:
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Nikolay Ninov; Cristina Manjón; Enrique Martín-Blanco |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: PLoS biology Volume: 7 ISSN: 1545-7885 ISO Abbreviation: PLoS Biol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-30 Completed Date: 2009-05-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101183755 Medline TA: PLoS Biol Country: United States |
Other Details:
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Languages: eng Pagination: e1000079 Citation Subset: IM |
Affiliation:
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Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism* Abdomen / growth & development Animals Cell Cycle / genetics, physiology Cell Division / physiology Cell Proliferation* Cell Size Cyclin E / metabolism Drosophila Proteins / genetics, metabolism* Drosophila melanogaster / cytology, growth & development*, metabolism Ecdysone / genetics, metabolism* Epidermis / cytology, growth & development Gene Expression Regulation, Developmental Larva Morphogenesis / physiology* Pupa Receptor, Epidermal Growth Factor / metabolism* Receptor, Insulin / metabolism Signal Transduction / physiology cdc25 Phosphatases / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclin E; 0/Drosophila Proteins; 3604-87-3/Ecdysone; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptor, Insulin; EC 3.1.3.48/cdc25 Phosphatases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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