whether there are oligodendrocyte abnormalities in these and other BD iPSC models is warranted. Finally, several results from our studies suggest WNT signaling is perturbed in the neural cells from the two BD affected sons. First, in both our NPCs and nEBs, we identified multiple genes involved in WNT signaling that were differentially expressed between the BD and parental lines. Second, rescue of the proliferation defect in the BD-patient NPCs from Family-811 upon treatment with CHIR-99021, a highly potent, and selective GSK3 inhibitor41, suggest dysregulation of the WNT pathway may underlie at least a subset of the phenotypic differences observed in the BD-patient NPCs. Given the ability of the BD therapeutic lithium to activate WNT signaling, these findings support the notion that targeting the WNT/GSK3 pathway may provide an important direction for the development of novel therapeutics for BD74.
