The first step in modeling cortical interneuron development is the robust induction of forebrain precursors. Specification of anterior/forebrain fate is considered a default program during neural differentiation of hPSCs (Chambers et al., 2009; Eiraku et al., 2008; Espuny-Camacho et al., 2013; Gaspard et al., 2008). However, not all cell lines adopt anterior neural fates at equal efficiencies (Kim et al., 2011; Wu et al., 2007). Patterning factors secreted within differentiating cultures such as fibroblast growth factors (FGFs), Wnts or retinoids can suppress forebrain induction and trigger the induction of caudal cell fates. We recently reported that early, high-dose SHH treatment also suppresses forebrain markers such as FOXG1 via inhibition of DKK1 induction (Fasano et al., 2010). This is a concern for deriving cortical interneurons that are thought to require strong SHH activation at the NKX2.1+ progenitor stage (Xu et al., 2010). Here we tested whether pharmacological inhibition of WNT signaling can improve FOXG1 induction and subsequently enable the controlled, SHH-mediated ventralization towards NKX2.1+ forebrain progenitor fates (Figure 1A).
