Figure 9.

A schematic presentation of cell fate control by the Lis1–Nde1 complex in radial glial progenitors, and its loss of functional defects. In normal metaphase radial glial progenitors, both the cell body and mitotic chromosomes are apically localized along the ventricular surface, and the cell is in close contact with neighboring progenitors. Such cellular architecture ensures the asymmetrical mitotic division and maintains the progenitor in proliferative state. In the Nde1^−/− and Nde1^+/−Lis1^+/− mutants, although many cells fail to position their mitotic chromosomes apically, large degree of apical cell–cell contacts still remains, resulting in moderate neurogenesis defects. Further loss of Lis1–Nde1 function in the Nde1^−/−Lis1^+/− progenitors results in destabilization of apical cell membrane and loss of cell–cell contacts. These changes in the cytoarchitecture of metaphase cells act collaboratively with the mitotic spindle orientation defects and induce striking shift of progenitor fate towards neuronal differentiation.