Both the narrow apical plasma membrane domain and the basal process that connects progenitors to the pial surface should be inherited

by only one daughter cell during oblique or vertical division. As BPs do not maintain their connection to the apical surface (Götz and Huttner, 2005 and Miyata et al., 2004) but do contain a basal process, the asymmetric inheritance of those structures could contribute to intermediate progenitor formation. For example, intermediate progenitors could simply move out of the VZ after S phase because they are click here not attached to the apical surface. Alternatively, apically localized proteins could perform a more direct signaling role. It has been proposed that the asymmetric inheritance of Par3 can activate Notch signaling in one daughter cell of an apical progenitor (Bultje et al., 2009). As levels of Notch signaling are lower in intermediate progenitors and decreasing levels of Notch signaling promotes the formation of intermediate progenitors (Mizutani et al., 2007 and Pierfelice et al., 2011), one could imagine

that the loss of Par3 during an oblique division establishes BP fate in one of the two daughter cells. Alternatively, the basal process could carry certain signaling molecules, whose selleck chemical asymmetric inheritance alters daughter cell fate (Schwamborn et al., 2009). How could mInsc act on a molecular level? In Drosophila, the expression of Insc recruits Pins to the apical cortex and acts as a molecular switch for spindle orientation. In the mouse cortex, however, progenitor cells seem to express equal levels of mInsc regardless of division orientation. It has been demonstrated that horizontal spindle orientation in epithelial cells depends on aPKC-mediated phosphorylation of LGN ( Hao et al., 2010). Assuming that a similar mechanism regulates horizontal spindles in the cortex, mInsc could simply inhibit this pathway by binding to the aPKC/Par-3/Par6 complex and thereby promote nonplanar orientation of the mitotic spindle. In this model, the role of mInsc would not be to instruct apical-basal orientation

in a binary manner but to introduce imprecision and cause a degree of stochasticity in the orientation of progenitor divisions. This would explain why mInsc expression levels do not decide on the Meloxicam orientation of individual progenitor divisions, but overall changes of mInsc expression have a strong influence on the fraction of cells that divide in a nonplanar fashion. It has been proposed that changes in spindle orientation have influenced cortical evolution (Bond et al., 2002, Fish et al., 2008 and Zhang, 2003). The gene Aspm, which is required for correct orientation of early proliferative neuroepithelial divisions ( Fish et al., 2008), has evolved adaptively in primates suggesting a functional alteration during primate evolution.