As would be expected, genetic perturbations of the three npBAF-specific subunits, BAF53a, BAF45a/d and SS18, also cause proliferation defects in NSCs. Knockdown of either BAF45a or BAF53a, or both, in E13.5 cortical cultures reduces the rate of BrdU incorporation without affecting cell survival or terminal differentiation (Lessard et al., 2007). Interestingly, while ES cells tolerate knockdown of SS18 to 20% of wild-type protein level, NSCs fail to self-renew when SS18 is decreased by only 20% (Staahl et al., 2013), indicating their heightened sensitivity to the levels of this subunit. Consistent with this, SS18+/− embryos are able to implant but die between E8.5 and E9.5 (de Bruijn et al., 2006). Importantly, perturbing neuron-specific subunits which are highly homologous to the npBAF subunits does not cause the same phenotype in NSCs. While overexpression of BAF45a causes a 2- to 4-fold increase in the number of cycling cortical and cerebellar progenitors at E14.5, ectopic BAF45b expression has no discernable effect (Lessard et al., 2007). Conversely, knockdown of BAF45a, but not BAF45b, leads to a reduced number of proliferative neural progenitors in the same
