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Chunk #25 — Discussion

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Modeling hippocampal neurogenesis using human pluripotent stem cells.
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PROX1 expression, although highly restricted to the DG of the hippocampus in the adult brain, can also be found in additional regions of the developing brain (Torii et al., 1999; Lavado and Oliver, 2007). However, a few key findings have identified PROX1 as a suitable marker to identify the target population of DG granule neurons in our differentiation approach. First, PROX1 is uniquely found in the DG of the developing forebrain (Lavado and Oliver, 2007). Recent studies have demonstrated the feasibility of obtaining an enriched population of dorsal forebrain precursors to generate cortical pyramidal neurons from hPSCs (Shi et al., 2012a; Vanderhaeghen, 2012). Our differentiation approach extends this to identify hippocampal neural progenitors expressing FOXG1, PAX6, EMX2, and NEUROD1, which have all been shown to be critical in the development of DG (Pellegrini et al., 1996; Schwab et al., 2000; Shinozaki et al., 2004; Shen et al., 2006; Osumi et al., 2008), thus providing the rationale for using PROX1 as a reliable marker to identify our target neuronal subtype. Furthermore, the temporal expression patterns of these transcription factors during the