Importantly, the defective astrocytic maturation of SCZ hGPCs might also have profound effects on developmental synaptogenesis and circuit formation, as well as on myelinogenesis. Neural connectivity and synaptic development are both intimately dependent upon astrocytic guidance (Clarke and Barres, 2013; Ullian et al., 2001), and hence upon the appropriate timing of astrocytic appearance and maturation. As a result, any disruption in astrocytic maturation by SCZ hGPCs, as observed in each of the SCZ lines we studied, might be expected to significantly confound the construction and functional architecture of those neural networks in which SCZ hGPCs are resident. Moreover, glial progenitors themselves may have significant interactions with local neurons (Sakry et al., 2014), such that their dysfunction might disrupt local neuronal response thresholds and circuit formation.
