title: Global programmed switch in neural daughter cell proliferation mode triggered by a temporal gene cascade.
abstract: During central nervous system (CNS) development, progenitors typically divide asymmetrically, renewing themselves while budding off daughter cells with more limited proliferative potential. Variation in daughter cell proliferation has a profound impact on CNS development and evolution, but the underlying mechanisms remain poorly understood. We find that Drosophila embryonic neural progenitors (neuroblasts) undergo a programmed daughter proliferation mode switch, from generating daughters that divide once (type I) to generating neurons directly (type 0). This typeI>0 switch is triggered by activation of Dacapo (mammalian p21(CIP1)/p27(KIP1)/p57(Kip2)) expression in neuroblasts. In the thoracic region, Dacapo expression is activated by the temporal cascade (castor) and the Hox gene Antennapedia. In addition, castor, Antennapedia, and the late temporal gene grainyhead act combinatorially to control the precise timing of neuroblast cell-cycle exit by repressing Cyclin E and E2f. This reveals a logical principle underlying progenitor and daughter cell proliferation control in the Drosophila CNS.
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
authors: Magnus
authors: M
authors: Baumgardt
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
authors: Daniel
authors: D
authors: Karlsson
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
authors: Behzad Y
authors: BY
authors: Salmani
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
authors: Caroline
authors: C
authors: Bivik
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
authors: Ryan B
authors: RB
authors: MacDonald
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
authors: Erika
authors: E
authors: Gunnar
authors: Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden. Electronic address: stefan.thor@liu.se.
authors: Stefan
authors: S
authors: Thor
mesh_terms: D000818:Animals; D051943:Antennapedia Homeodomain Protein / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005812:Genes, Switch; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D019927:Cyclin E; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C110593:cas protein, Drosophila; C103336:dap protein, Drosophila; C062330:grh protein, Drosophila