Biochemical analysis revealed that loss of Mmd2 in the chick spinal cord results in decreased activity of respiratory chain complexes

II and IV, thus correlating the proliferation of glial progenitors with energy metabolism. Indeed, electron transport chain function has previously been linked to cell cycle regulators and proliferation; therefore, it will be important to decipher the relationship between complex II/IV, cell proliferative mechanisms, and glial precursor biology ( Mandal et al., 2010 and Schauen et al., 2006). Moreover, that Mmd2 appears to regulate energy metabolism via complex II/IV and is induced just after glial specification suggests that glial precursors have unique energy and/or metabolic requirements that are distinct from neural stem cells and committed neuronal learn more progenitors. It is likely that each of these cell populations have unique metabolic Birinapant solubility dmso profiles that reflect their biology and/or impending lineage commitments; indeed, neurons, astrocytes, and oligodendrocytes each have distinct metabolic requirements. Interestingly, the timing of cardiac myocyte differentiation has been linked to mitochondria maturation and function, indicating that metabolic function participates in lineage development

( Hom et al., 2011). Therefore, in the future it will be important to identify distinct metabolic features of these precursor populations and to further delineate how these processes are coordinated with transcriptional cascades that specify their identity. Apcdd1 is a membrane-bound glycoprotein that can inhibit canonical Wnt signaling through association with Wnt receptor complexes, though its exact role during spinal cord development remains undefined ( Shimomura et al., 2010). These previous studies revealed a mild effect of Apcdd1-L9R on proliferation and specification during neurogenesis, enough phenotypes that we did

not observe during gliogenesis ( Figures 7 and S8), probably reflecting stage-specific effects of Apcdd1-L9R. Our studies indicate that Apcdd1 plays a key role in the migration of ASP populations, probably through an association with Rho-GTPases. The observation that Apcdd1 can influence Wnt receptor complexes, coupled with the role of noncanonical Wnt signaling in cell migration and regulation of Rho-GTPases, suggest a model whereby Apcdd1 could function to promote ASP migration via noncanonical Wnt signaling ( Schlessinger et al., 2009). That L9R overexpression does not effect the generation of ASP populations in the VZ suggests that Apcdd1 is either not necessary for the generation of these populations or functions through other mechanisms. Alternatively, the epithelial to mesenchymal transition (EMT) has been shown to promote migration and the acquisition of progenitor-like states ( Mani et al., 2008 and Acloque et al., 2009).