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Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis

Abstract

During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions1,2, its role in mammalian neurogenesis remains unclear. Here we show that control of spindle orientation is essential in maintaining the population of neuroepithelial cells, but dispensable for the decision to either proliferate or differentiate. Knocking out LGN, (the G protein regulator)3,4, randomized the orientation of normally planar neuroepithelial divisions. The resultant loss of the apical membrane from daughter cells frequently converted them into abnormally localized progenitors without affecting neuronal production rate. Furthermore, overexpression of Inscuteable5 to induce vertical neuroepithelial divisions shifted the fate of daughter cells. Our results suggest that planar mitosis ensures the self-renewal of neuroepithelial progenitors by one daughter inheriting both apical and basal compartments during neurogenesis.

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Figure 1: Neuroepithelial cells undergo planar divisions in developing brains.
Figure 2: Loss of LGN function randomizes spindle orientation and induces non-surface progenitors at the expense of the apical progenitors.
Figure 3: Insc expression in the ventricular zone randomizes spindle orientation.
Figure 4: Time-lapse analysis of apical surface inheritance during apical progenitor divisions.
Figure 5: Vertical neuroepithelial divisions confer biased cell fates to daughters.

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Acknowledgements

We thank A. Miyawaki (RIKEN, Saitama, Japan) for providing the Venus gene, Y. Hayashizaki (RIKEN, Saitama, Japan) for FANTOM3 clones, K. Nakao (RIKEN, Kobe, Japan) for targeting mice, T. Saito (Chiba University, Chiba, Japan) for technical advice, and members of the Matsuzaki laboratory for helpful discussions.

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Correspondence to Fumio Matsuzaki.

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Konno, D., Shioi, G., Shitamukai, A. et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol 10, 93–101 (2008). https://doi.org/10.1038/ncb1673

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