title: The p21-activated kinase Mbt is a component of the apical protein complex in central brain neuroblasts and controls cell proliferation.
abstract: The final size of the central nervous system is determined by precisely controlled generation, proliferation and death of neural stem cells. We show here that the Drosophila PAK protein Mushroom bodies tiny (Mbt) is expressed in central brain progenitor cells (neuroblasts) and becomes enriched to the apical cortex of neuroblasts in a cell cycle- and Cdc42-dependent manner. Using mushroom body neuroblasts as a model system, we demonstrate that in the absence of Mbt function, neuroblasts and their progeny are correctly specified and are able to generate different neuron subclasses as in the wild type, but are impaired in their proliferation activity throughout development. In general, loss of Mbt function does not interfere with establishment or maintenance of cell polarity, orientation of the mitotic spindle and organization of the actin or tubulin cytoskeleton in central brain neuroblasts. However, we show that mbt mutant neuroblasts are significantly reduced in cell size during different stages of development, which is most pronounced for mushroom body neuroblasts. This phenotype correlates with reduced mitotic activity throughout development. Additionally, postembryonic neuroblasts are lost prematurely owing to apoptosis. Yet, preventing apoptosis did not rescue the loss of neurons seen in the adult mushroom body of mbt mutants. From these results, we conclude that Mbt is part of a regulatory network that is required for neuroblast growth and thereby allows proper proliferation of neuroblasts throughout development.
authors.affiliation: Universität Würzburg, Institut für Medizinische Strahlenkunde und Zellforschung, Versbacherstrasse 5, Würzburg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Melzer
authors.forename: Karoline F
authors.initials: KF
authors.lastname: Kraft
authors.forename: Rolf
authors.initials: R
authors.lastname: Urbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Raabe
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D060049:Asymmetric Cell Division; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000201:enzymology; D002452:Cell Count; D016764:Cell Polarity; D049109:Cell Proliferation; D048429:Cell Size; D004330:Drosophila / Q000166:cytology* / Q000196:embryology / Q000201:enzymology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000166:cytology / Q000201:enzymology; D008938:Mitosis; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000201:enzymology*; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: C090145:Cdc42 protein, Drosophila; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D014404:Tubulin; D011494:Protein Kinases; C116684:mbt protein, Drosophila; D019204:GTP-Binding Proteins