Development
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Many genes regulating adult neurogenesis have been identified and are known to play similar roles during early neuronal development. We recently identified apolipoprotein E (ApoE) as a gene the expression of which is essentially absent in early brain progenitors but becomes markedly upregulated in adult dentate gyrus stem/progenitor cells. Here, we demonstrate that ApoE deficiency impairs adult dentate gyrus development by affecting the neural progenitor pool over time. ⋯ This appears to be secondary to over-proliferation early in life and ultimate depletion of the Type 1 nestin- and GFAP-expressing neural stem cells. We also rescue the proliferation phenotype with an ApoE-expressing retrovirus, demonstrating that ApoE works directly in this regard. These data provide novel insight into late hippocampal development and suggest a possible role for ApoE in neurodegenerative diseases.