Key role played by RhoA in the balance between planar and apico-basal cell divisions in the chick neuroepithelium

The cell division axis determines the position of daughter cells and is therefore critical for cell fate. During vertebrate neurogenesis, most cell divisions take place within the plane of the neuroepithelium (Das, T., Payer, B., Cayouette, M., and Harris, W.A. (2003). In vivo time-lapse imaging of cell divisions during neurogenesis in the developing zebrafish retina. Neuron 37, 597-609. Haydar, T.F., Ang, E., Jr., and Rakic, P. (2003). Mitotic spindle rotation and mode of cell division in the developing telencephalon. Proc Natl Acad Sci U S A 100, 2890-5. Kosodo, Y., Roper, K., Haubensak, W., Marzesco, A. M., Corbeil, D., and Huttner, W. B. (2004). Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO J. 23, 2314-24). The cellular constraints responsible for this preferential orientation are poorly understood. Combining electroporation and time-lapse confocal imaging of chick neural progenitors, the events responsible for positioning the mitotic spindle and their dependence on RhoA were investigated. The results indicate that the spindle forms with a random orientation. However, the final orientation of cell divisions is dependent on two main factors: (i) an early rotation of the spindle that aligns it within the plane of the neuroepithelium, and (ii) a specific limitation of spindle oscillations, despite free rotation around the apico-basal axis. Expressing a dominant-negative RhoA leads to apico-basal cell divisions after a correct initial rotation of the spindle. Our data reveal a specific role for RhoA in the maintenance of spindle orientation, prior to anaphase. Thus, RhoA could be a key player potentially regulated by the neurogenic program or by the neural stem cell environment to control the balance between planar and apico-basal divisions, during normal or pathological development.