Dynamic centriolar localization of Polo and Centrobin in early mitosis primes centrosome asymmetry

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.

Centrosome-centric view of asymmetric stem cell division

“…Multiple mechanisms contribute to creating the asymmetry between the mother and daughter centrosomes in Drosophila neuroblasts. The daughter centrosome's MTOC activity is upregulated by recruitment of Cnb and Polo, which occurs during mitosis in preparation for centrosome asymmetry in the next interphase [ 45 , 46 ]. In parallel, the mother centrosome's MTOC activity is downregulated, releasing it from the apical cortex, leading to its eventual inheritance by the differentiating cell.…”

PLK-1 Regulation of Asymmetric Cell Division in the Early C. elegans Embryo

“…In polo mutants, Pon and Numb are not asymmetrically localized to basal cortex, causing a failure of asymmetric division that leads to neuroblast over-proliferation. Additionally, increased Polo activity at the daughter centrosomes relative to mother centrosomes is essential for the retention of the daughter centrosome in the neuroblast cell following cell division (Januschke et al, 2013 ; Conduit et al, 2014 ; Gallaud et al, 2020 ). The extent to which the resulting asymmetric inheritance of mother and daughter centrosomes regulates the fate of apical and basal daughter cells remains an open area of investigation.…”

Optogenetic approaches for understanding homeostatic and degenerative processes in Drosophila

“…For example, morphogenesis during embryonic Drosophila development has been studied using optogenetics in a variety of ways [ 90 ]. A non-exhaustive list of optogenetic approaches to study Drosophila development includes: the structure of centrosomes [ 91 ], Erk signalling [ 27 , 92 – 94 ], Toll signalling [ 95 ], adhesion [ 56 , 96 – 98 ], cell shapes [ 99 ], GTPase activity [ 45 , 100 – 110 ], anterior-to-posterior patterning through Bicoid [ 111 ], Wnt [ 112 ], and Notch signalling [ 113 ]. One approach that looked at phosphatidylinosital-4,5 biphosphate [PI(4,5)P2] during Drosophila ventral furrow formation showed that it was required for apical constriction, an essential tissue invagination process [ 114 , 115 ].…”