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Chunk #30 — DISCUSSION

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Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells.
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Past studies have reported species differences in cortical interneuron development, based on the presence of ASCL1+ cells within the second trimester human fetal cortex (Letinic et al., 2002). Those data led to the hypothesis that many, and perhaps most human cortical interneurons are born within the cortex itself (Letinic et al., 2002). In contrast, studies in the mouse have demonstrated a subcortical origin of most if not all cortical interneurons (Fogarty et al., 2007; Xu et al., 2004). While our study was not specifically geared towards addressing this issue, we found restricted NKX2.1 expression within the ventral forebrain in CS15 human embryo and a complete lack of expression in the dorsal forebrain (see also Allen Brain Atlas, http://human.brain-map.org/). Furthermore, the ability of hESC-derived cortical interneurons to migrate in our slice culture assay and the developing murine cortex in vivo suggests that human cortical interneuron precursors have a similar capacity for tangential migration as their mouse counterparts. However, a distinctive feature in hESC-derived cortical interneurons was the persistent expression of NKX2.1. Nkx2.1 is extinguished in mouse cortical interneuron precursors by the