title: Retinal homeobox promotes cell growth, proliferation and survival of mushroom body neuroblasts in the Drosophila brain.
abstract: The Drosophila mushroom bodies, centers of olfactory learning and memory in the fly 'forebrain', develop from a set of neural stem cells (neuroblasts) that generate a large number of Kenyon cells (KCs) during sustained cell divisions from embryonic to late pupal stage. We show that retinal homeobox (rx), encoding for an evolutionarily conserved transcription factor, is required for proper development of the mushroom bodies. Throughout development rx is expressed in mushroom body neuroblasts (MBNBs), their ganglion mother cells (MB-GMCs) and young KCs. In the absence of rx function, MBNBs form correctly but exhibit a reduction in cell size and mitotic activity, whereas overexpression of rx increases growth of MBNBs. These data suggest that Rx is involved in the control of MBNB growth and proliferation. Rx also promotes cell cycling of MB-GMCs. Moreover, we show that Rx is important for the survival of MBNBs and Kenyon cells which undergo premature cell death in the absence of rx function. Simultaneous blocking of cell death restores the normal set of MBNBs and part of the KCs, demonstrating that both, impaired proliferation and premature cell death (of MBNBs and KCs) account for the observed defects in mushroom body development. We then show that Rx controls proliferation within the MBNB clones independently of Tailless (Tll) and Prospero (Pros), and does not regulate the expression of other key regulators of MB development, Eyeless (Ey) and Dachshund (Dac). Our data support that the role of Rx in forebrain development is conserved between vertebrates and fly.
authors.affiliation: Institute of Genetics, University of Mainz, D-55099 Mainz, Germany.
authors.forename: Karoline F
authors.initials: KF
authors.lastname: Kraft
authors.affiliation: Institute of Genetics, University of Mainz, D-55099 Mainz, Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Massey
authors.affiliation: Institute of Developmental Biology, Saarland University, D-66421 Homburg/Saar, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Kolb
authors.affiliation: Institute of Developmental Biology, Saarland University, D-66421 Homburg/Saar, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Walldorf
authors.affiliation: Institute of Genetics, University of Mainz, D-55099 Mainz, Germany. Electronic address: urbach@uni-mainz.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Urbach
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D045888:Ganglion Cysts / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development; D024521:Mushroom Bodies / Q000254:growth & development / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D058953:Neural Stem Cells / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012160:Retina / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C111250:Rx protein, Drosophila; C074090:TLL protein, Drosophila; D014157:Transcription Factors; C073099:pros protein, Drosophila
keywords: Cell death; Cell growth; Drosophila brain; Mushroom body neuroblast; Retinal homeobox (rx); Stem cell proliferation