title: Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells.
abstract: Stem cells are highly abundant during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone ecdysone and the Mediator initiate an irreversible cascade of events leading to cell-cycle exit in Drosophila neural stem cells. We show that the timely induction of oxidative phosphorylation and the mitochondrial respiratory chain are required in neuroblasts to uncouple the cell cycle from cell growth. This results in a progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Brain tumor mutant neuroblasts fail to undergo this shrinkage process and continue to proliferate until adulthood. Our findings show that cell size control can be modified by systemic hormonal signaling and reveal a unique connection between metabolism and proliferation in stem cells.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Catarina C F
authors.initials: CCF
authors.lastname: Homem
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Victoria
authors.initials: V
authors.lastname: Steinmann
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Burkard
authors.affiliation: Department of Laboratory Medicine, Medical University Vienna, 1090 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jais
authors.affiliation: Department of Laboratory Medicine, Medical University Vienna, 1090 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria. Electronic address: juergen.knoblich@imba.oeaw.ac.at.
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D048429:Cell Size; D004331:Drosophila melanogaster / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D004440:Ecdysone / Q000378:metabolism*; D004734:Energy Metabolism; D049750:Genome, Insect; D056892:Mediator Complex / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D056892:Mediator Complex; D004440:Ecdysone