title: ApoE is required for maintenance of the dentate gyrus neural progenitor pool.
abstract: 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. We utilized ApoE-deficient mice crossed to a nestin-GFP reporter to demonstrate that dentate gyrus progenitor cells proliferate more rapidly at early ages, which is subsequently accompanied by an overall decrease in neural progenitor cell number at later time points. 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.
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
authors: Cui-Ping
authors: CP
authors: Yang
authors: Jennifer A
authors: JA
authors: Gilley
authors: Gui
authors: G
authors: Zhang
authors: Steven G
authors: SG
authors: Kernie
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins