Abstract:
Centrosomes, the main microtubule organizing centers (MTOCs) of metazoan cells, contain
an older “mother” and a younger “daughter” centriole. Stem cells either inherit the mother or
daughter-centriole-containing centrosome, providing a possible mechanism for biased delivery of cell fate determinants. However, the mechanisms regulating centrosome asymmetry
and biased centrosome segregation are unclear. Using 3D-structured illumination microscopy (3D-SIM) and live-cell imaging, we show in fly neural stem cells (neuroblasts) that the
mitotic kinase Polo and its centriolar protein substrate Centrobin (Cnb) accumulate on the
daughter centriole during mitosis, thereby generating molecularly distinct mother and
daughter centrioles before interphase. Cnb’s asymmetric localization, potentially involving a
direct relocalization mechanism, is regulated by Polo-mediated phosphorylation, whereas
Polo’s daughter centriole enrichment requires both Wdr62 and Cnb. Based on optogenetic
protein mislocalization experiments, we propose that the establishment of centriole asymmetry in mitosis primes biased interphase MTOC activity, necessary for correct spindle
orientation.