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cdc2 links the Drosophila cell cycle and asymmetric division machineries

Abstract

Asymmetric cell divisions can be mediated by the preferential segregation of cell-fate determinants into one of two sibling daughters. In Drosophila neural progenitors, Inscuteable1,2,3, Partner of Inscuteable4,5 and Bazooka6,7 localize as an apical cortical complex at interphase, which directs the apical–basal orientation of the mitotic spindle as well as the basal/cortical localization of the cell-fate determinants Numb8,9 and/or Prospero10,11 during mitosis. Although localization of these proteins shows dependence on the cell cycle, the involvement of cell-cycle components in asymmetric divisions has not been demonstrated. Here we show that neural progenitor asymmetric divisions require the cell-cycle regulator cdc2. By attenuating Drosophila cdc2 function without blocking mitosis, normally asymmetric progenitor divisions become defective, failing to correctly localize asymmetric components during mitosis and/or to resolve distinct sibling fates. cdc2 is not necessary for initiating apical complex formation during interphase; however, maintaining the asymmetric localization of the apical components during mitosis requires Cdc2/B-type cyclin complexes. Our findings link cdc2 with asymmetric divisions, and explain why the asymmetric localization of molecules like Inscuteable show cell-cycle dependence.

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Figure 1: Conversion of asymmetric to symmetric divisions in cdc2 mutants.
Figure 2: Defective protein localization in dividing neural progenitors of cdc2 mutants.
Figure 3: Cdc2 kinase activity is required for the maintenance but not the establishment of Insc apical localization.
Figure 4: Cdc2 kinase activity is required for asymmetric cell divisions.

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Acknowledgements

We thank C. Q. Doe, M. Frasch, D. Glover, M. Harrington, Y.-N. Jan, E. Knust, Z. Lai, K. Matthews, F. Matsuzaki, P. O'Farrell, R. Saint, K. Zinn, the Developmental Studies Hybridoma Bank, Bloomington and Umea Stock Centres, and C. Lehner in particular for stocks and antibodies; F. S. Hing and C. T. Ong for technical support; M. Zavortink, U. Surana and members of our laboratory for comments and discussions; and IMCB for financial support. G.U. is supported by the Wellcome Trust.

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Correspondence to William Chia.

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Tio, M., Udolph, G., Yang, X. et al. cdc2 links the Drosophila cell cycle and asymmetric division machineries. Nature 409, 1063–1067 (2001). https://doi.org/10.1038/35059124

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