A recent paper demonstrated the importance of SHH dosage during in vitro ventral forebrain specification towards GSX2+, NKX2.1-negative progenitors capable of generating medium spiny striatal neurons (Ma et al., 2012). In addition to SHH-dose, timing can also affect the efficiency of ventral cell fate specification (Fasano et al., 2010). A remarkable feature of the current study is that the difference in timing of SHH activation is sufficient to trigger the generation of distinct ventral progenitors of divergent anterior-posterior identity. We have previously reported the derivation of hESC-derived progenitors expressing markers of the hypothalamic anlage (Kriks et al., 2011) following early activation of SHH signaling in the presence of FGF8. Our day 2-18 data suggest that addition of FGF8 is not critical for directing hypothalamic progenitor fate. Cholinergic neuron derivation from NKX2.1::GFP+ progenitors of the 6-18 group, should be of great value for modeling and treating disorders associated with loss of cognitive function. For example in Alzheimer’s disease basal forebrain cholinergic neurons are amongst the neurons most vulnerable during early stages of the disease (Whitehouse et al., 1982). However, the main focus of the current study is the derivation of human cortical interneuron lineages triggered in the day 10-18 protocol
