Our data demonstrate that in the spinal cord, the level of N-cadherin expression is not uniform but rather varies markedly between different progenitor groups along the dorsoventral axis in accordance to their expression of Foxp4. How might discrepancies in cadherin expression affect NPC function? Studies of germline stem cells in the Drosophila have shown that the level of E-cadherin plays

an important role in sustaining the stem cell pool and gating their differentiation behavior ( Song et al., 2002 and Voog et al., 2008). When E-cadherin function is blocked, germline stem cells lose contact with their niche and prematurely differentiate ( Song et al., 2002 and Voog et al., 2008). Remarkably, as little as JQ1 2-fold differences in E-cadherin levels can influence whether a germline stem cell remains in contact with the niche or differentiates ( Jin et al., 2008). Moreover, cells that express higher levels of E-cadherin can displace other cells from selleck products the niche, thus favoring the expansion of E-cadherinhigh cells over time ( Jin et al., 2008). By analogy, groups of vertebrate NPCs that express lower or higher levels of N-cadherin might have different adhesive properties, which could similarly influence their self-renewal capacity and

propensity for differentiation. The reduced expression of N-cadherin in the pMN, for example, could explain why MNs are among the first cells to differentiate in the spinal Rebamipide cord and why pMN cells rapidly lose their stem cell characteristics when grown in vitro compared to other progenitor groups ( Mukouyama et al., 2006). The differential expression of cadherins may thus be one way in which

the morphogen signals that pattern the developing nervous system ensure that different populations of NPCs expand and differentiate in a stereotyped manner. In many tissues, the expansion of the stem cell pool is proportional to the size and numbers of cells that make up the niche. If the niche is enlarged or contracted, stem cell numbers are accordingly changed (Voog and Jones, 2010). In the embryonic nervous system, NPCs do not depend upon support cells; rather they form their own niche microenvironment through AJs contacts within the neuroepithelium (Zhang et al., 2010). These observations raise the question of whether there are comparable mechanisms for limiting the “size” of the NPC niche and expansion of progenitors. Our data suggest that the transcriptional regulation of N-cadherin is a means by which the embryonic NPC niche could be regulated. Previous work by Kondoh and colleagues has shown that Sox2 directly activates N-cadherin expression (Matsumata et al., 2005). Our results extend those findings by identifying Foxp4 binding sites in the Cdh2 locus that likely mediate its repressive effects on N-cadherin.