Asymmetric cell division during brain morphogenesis.

Abstract

The division patterns of neural progenitor cells in developing vertebrate brains have traditionally been classified into three types: (i) "symmetric" divisions producing two progenitor cells (P/P division), (ii) "symmetric" divisions producing two neurons (N/N division), and (iii) "asymmetric" divisions producing one progenitor cell and one neuron (P/N division). Many studies examining the mechanism(s) regulating P/N divisions have focused on mitotic cleavage orientation and the possible uneven distribution of cell-fate determining molecules such as Numb. Although these two factors may intrinsically determine daughter cell fate arising from M-phase progenitor cells, no unified explanations have yet to be put forth incorporating all available data. In this review, I will discuss recent advances in techniques allowing the more detailed monitoring of daughter cell behavior in a heterogeneously pseudostratified neuroepithelium that demonstrate previously unrecognized asymmetries in P/P divisions. Careful observations of daughter cell behavior suggest that, immediately after their birth at the apical surface of the neuroepithelium, generated cells may not yet be fate committed but rather integrate extrinsic and intrinsic signals during GI phase before continuing down a developmental pathway.