Mcm3 replicative helicase mutation impairs neuroblast proliferation and memory in Drosophila.
In the developing Drosophila brain, a small number of neural progenitor cells (neuroblasts) generate in a co-ordinated manner a high variety of neuronal cells by integration of temporal, spatial and cell-intrinsic information. In this study, we performed the molecular and phenotypic characterization of a structural brain mutant called small mushroom bodies (smu), which was isolated in a screen for mutants with altered brain structure. Focusing on the mushroom body neuroblast lineages we show that failure of neuroblasts to generate the normal number of mushroom body neurons (Kenyon cells) is the major cause of the smu phenotype. In particular, the premature loss of mushroom body neuroblasts caused a pronounced effect on the number of late-born Kenyon cells. Neuroblasts showed no obvious defects in processes controlling asymmetric cell division, but generated less ganglion mother cells. Cloning of smu uncovered a single amino acid substitution in an evolutionarily conserved protein interaction domain of the Minichromosome maintenance 3 (Mcm3) protein. Mcm3 is part of the multimeric Cdc45/Mcm/GINS (CMG) complex, which functions as a helicase during DNA replication. We propose that at least in the case of mushroom body neuroblasts, timely replication is not only required for continuous proliferation but also for their survival. The absence of Kenyon cells in smu reduced learning and early phases of conditioned olfactory memory. Corresponding to the absence of late-born Kenyon cells projecting to α'/β' and α/β lobes, smu is profoundly defective in later phases of persistent memory.
Institute of Medical Radiation and Cell Research, University of Würzburg, Germany.
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Blumröder
Institute of Medical Radiation and Cell Research, University of Würzburg, Germany.
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Glunz
School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA.|Present address: Las Vegas High School, Las Vegas, NV, USA.
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Dunkelberger
School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA.|Present address: UNM Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.
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Serway
Institute of Medical Radiation and Cell Research, University of Würzburg, Germany.
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Berger
Institute of Medical Radiation and Cell Research, University of Würzburg, Germany.|Present address: State of Lower Saxony, Ministry of the Environment, Energy and Climate Protection, Hannover, Germany.
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Mentzel
School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA.|Present address: Dart Neuroscience LLC, San Diego, CA, USA.
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de Belle
Institute of Medical Radiation and Cell Research, University of Würzburg, Germany. thomas.raabe@mail.uni-wuerzburg.de.
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Raabe
D000818:Animals; D001921:Brain / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila; D008568:Memory / Q000502:physiology; D064126:Minichromosome Maintenance Complex Component 3 / Q000235:genetics* / Q000378:metabolism; D024521:Mushroom Bodies / Q000378:metabolism; D009154:Mutation; D058953:Neural Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000502:physiology
D004265:DNA Helicases; D064126:Minichromosome Maintenance Complex Component 3
Associative olfactory memory; CMG helicase; Drosophila; Kenyon cells; Mcm3; mushroom body; neuroblast; proliferation