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Publication : The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex.

First Author  Xie Y Year  2013
Journal  Neuron Volume  79
Issue  2 Pages  254-65
PubMed ID  23830831 Mgi Jnum  J:201674
Mgi Id  MGI:5515261 Doi  10.1016/j.neuron.2013.05.027
Citation  Xie Y, et al. (2013) The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex. Neuron 79(2):254-65
abstractText  In the developing neocortex, progenitor cells expand through symmetric division before they generate cortical neurons through multiple rounds of asymmetric cell division. Here, we show that the orientation of the mitotic spindle plays a crucial role in regulating the transition between those two division modes. We demonstrate that the protein phosphatase PP4c regulates spindle orientation in early cortical progenitor cells. Upon removing PP4c, mitotic spindles fail to orient in parallel to the neuroepithelial surface and progenitors divide with random orientation. As a result, their divisions become asymmetric and neurogenesis starts prematurely. Biochemical and genetic experiments show that PP4c acts by dephosphorylating the microtubule binding protein Ndel1, thereby enabling complex formation with Lis1 to form a functional spindle orientation complex. Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division.
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