The Centriolar Protein Bld10/Cep135 Is Required to Establish Centrosome Asymmetry in Drosophila Neuroblasts

• Drosophila neuroblasts establish centrosome asymmetry through PCM shedding
• The centriolar protein Bld10/Cep135 is required to establish centrosome asymmetry
• Bld10 promotes shedding of Polo and PCM at the basal centrosome during interphase
• Centrosome asymmetry is required for spindle orientation and centrosome segregation

SummaryCentrosome asymmetry has been implicated in stem cell fate maintenance in both flies and vertebrates [1 and 2]. Drosophila neuroblasts, the neural precursors of the fly’s central nervous system [ 3], contain molecularly and physically asymmetric centrosomes, established through differences in pericentriolar matrix (PCM) retention [ 4, 5, 6 and 7]. For instance, the daughter centriole maintains PCM and thus microtubule-organizing center (MTOC) activity through Polo-mediated phosphorylation of Centrobin (Cnb) [ 7 and 8]. The mother centriole, however, quickly downregulates PCM and moves away from the apical cortex, randomly migrating through the cytoplasm until maturation sets in at prophase [ 4, 5, 6 and 8]. How PCM downregulation is molecularly controlled is currently unknown, but it involves Pericentrin (PCNT)-like protein (PLP) to prevent premature Polo localization and thus MTOC activity [9]. Here, we report that the centriolar protein Bld10, the fly ortholog of Cep135, is required to establish centrosome asymmetry in Drosophila neuroblasts through shedding of Polo from the mother centrosome. bld10 mutants fail to downregulate Polo and PCM, generating two active, improperly positioned MTOCs. Failure to shed Polo and PCM causes spindle alignment and centrosome segregation defects, resulting in neuroblasts incorrectly retaining the older mother centrosome. Since Cep135 is implicated in primary microcephaly, we speculate that perturbed centrosome asymmetry could contribute to this rare neurodevelopmental disease.

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