These studies have identified a set of intrinsic polarity regulators, which function to ensure proper segregation of cell fate determinants into two daughter cells (Doe, 2008, Guo and Kemphues, 1996, Knoblich, 2010 and Lu et al., 2000). Compared to these advances, much less is understood about the regulation of asymmetric cell division and subsequent daughter cell fate choice in vertebrates. Despite that conserved counterparts to the invertebrate genes are found in vertebrates, the function of these proteins is only beginning to be elucidated (Doe, Alectinib research buy 2008, Götz and Huttner, 2005, Knoblich, 2010 and Williams et al., 2011). Available data suggest that vertebrates

may deploy these factors in new and different ways that remain enigmatic.

Radial glia in the developing vertebrate central nervous system (CNS) have stem cell-like properties (Götz and Huttner, 2005, Kriegstein and Alvarez-Buylla, 2009, Malatesta et al., 2000, Miyata et al., 2001, Noctor et al., 2001 and Temple, 2001). Previous studies in mammals (Bultje et al., 2009, Cayouette et al., 2001, Chenn and McConnell, 1995, Miyata et al., 2001, Miyata et al., Pifithrin �� 2004 and Noctor et al., 2004) and zebrafish (Alexandre et al., 2010, Baye and Link, 2007 and Das et al., 2003) show that during the peak phase of neurogenesis, radial glia progenitors predominantly undergo asymmetric divisions, serving as an excellent model for understanding how asymmetric cell division, self-renewal, and differentiation are regulated in vertebrate ALOX15 stem cells. An interesting behavior that vertebrate radial glia progenitors display is the interkinetic nuclear migration (INM) (Baye and Link, 2008, Miyata, 2008 and Sauer, 1935), which refers to the movement of progenitor nuclei between the apical and basal surfaces of the neuroepithelium in phase with their cell cycle. Studies in the developing chick CNS (Murciano et al., 2002) and zebrafish retina (Baye and Link, 2007 and Del Bene et al., 2008) suggest that proliferative (self-renewing) versus neurogenic (differentiating)

potential of radial glia progenitors is largely determined by their pattern of INM. In particular, Del Bene et al. (2008) proposes the presence of a Notch gradient between the apical and basal surfaces of the neuroepithelium, raising the possibility that extrinsic signals play a critical role in determining vertebrate progenitor self-renewal or differentiation in a location-dependent manner. Here, we carry out in vivo time-lapse imaging with single-cell resolution and perform clonal genetic mosaic analysis of individual radial glia lineages in the developing zebrafish brain. Our study uncovers a stereotyped pattern of asymmetric division that invariably generates a self-renewing daughter that migrates to a basal position and a differentiating sibling remaining at the apical position.