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Chunk #1 — INTRODUCTION

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Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells.
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al., 2010; Pasca et al., 2011). Unlike in PD, ALS or SMA, the neuron types critical for modeling schizophrenia or autism are less well defined, and no attempts have been made to direct neuron subtype identity in those studies. There has been considerable progress in establishing protocols for the derivation of human ESC-derived cortical projection neurons (Espuny-Camacho et al., 2013; Shi et al., 2012). However, inhibitory neurons, such as cortical interneurons may be particularly important in schizophrenia or autism (Insel, 2010; Lewis et al., 2005). We have previously demonstrated the derivation of cortical interneurons using a Lhx6::GFP reporter mouse ESC line (Maroof et al., 2010). However, the efficiency of cortical interneuron generation was low, and it was uncertain whether those conditions would apply for generating human cortical interneurons from PSCs. Modeling human cortical interneuron development in vitro is of particular interest as their developmental origin is controversial with studies suggesting considerable differences across mammalian species (Letinic et al., 2002; Yu and Zecevic, 2011). Furthermore, the protracted in vivo development of several cortical interneuron types (Anderson et al., 1995), represents an additional challenge for modeling their differentiation using human cells in vitro.