title: The Microcephaly-Associated Protein Wdr62/CG7337 Is Required to Maintain Centrosome Asymmetry in Drosophila Neuroblasts.
abstract: Centrosome asymmetry has been implicated in stem cell fate maintenance in both flies and vertebrates, but the underlying molecular mechanisms are incompletely understood. Here, we report that loss of CG7337, the fly ortholog of WDR62, compromises interphase centrosome asymmetry in fly neural stem cells (neuroblasts). Wdr62 maintains an active interphase microtubule-organizing center (MTOC) by stabilizing microtubules (MTs), which are necessary for sustained recruitment of Polo/Plk1 to the pericentriolar matrix (PCM) and downregulation of Pericentrin-like protein (Plp). The loss of an active MTOC in wdr62 mutants compromises centrosome positioning, spindle orientation, and biased centrosome segregation. wdr62 mutant flies also have an ∼40% reduction in brain size as a result of cell-cycle delays. We propose that CG7337/Wdr62, a microtubule-associated protein, is required for the maintenance of interphase microtubules, thereby regulating centrosomal Polo and Plp levels. Independent of this function, Wdr62 is also required for the timely mitotic entry of neural stem cells.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Anjana
authors.initials: A
authors.lastname: Ramdas Nair
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Salvador Garcia
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Crespo
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Boris
authors.initials: B
authors.lastname: Egger
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland. Electronic address: clemens.cabernard@unibas.ch.
authors.forename: Clemens
authors.initials: C
authors.lastname: Cabernard
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D006801:Humans; D007399:Interphase; D008831:Microcephaly / Q000378:metabolism*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C552527:WDR62 protein, human; C000611882:Wdr62 protein, Drosophila