title: Neurogenin 2 mediates amyloid-β precursor protein-stimulated neurogenesis.
abstract: Amyloid-β precursor protein (APP) is well studied for its role in Alzheimer disease, although its normal function remains uncertain. It has been reported that APP stimulates the proliferation and neuronal differentiation of neural stem/progenitor cells (NSPCs). In this study we examined the role of APP in NSPC differentiation. To identify proteins that may mediate the effect of APP on NSPC differentiation, we used a gene array approach to find genes whose expression correlated with APP-induced neurogenesis. We found that the expression of neurogenin 2 (Ngn2), a basic helix-loop-helix transcription factor, was significantly down-regulated in NSPCs from APP knock-out mice (APPKO) and increased in APP transgenic (Tg2576) mice. Ngn2 overexpression in APPKO NSPCs promoted neuronal differentiation, whereas siRNA knockdown of Ngn2 expression in wild-type NSPCs decreased neuronal differentiation. The results demonstrate that APP-stimulated neuronal differentiation of NSPCs is mediated by Ngn2.
authors.affiliation: From the Menzies Research Institute Tasmania and.
authors.forename: Marta
authors.initials: M
authors.lastname: Bolós
authors.affiliation: From the Menzies Research Institute Tasmania and.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.affiliation: From the Menzies Research Institute Tasmania and.
authors.forename: Kaylene M
authors.initials: KM
authors.lastname: Young
authors.affiliation: From the Menzies Research Institute Tasmania and School of Medicine, University of Tasmania, Hobart, Tasmania 7000, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Foa
authors.affiliation: From the Menzies Research Institute Tasmania and d.h.small@menzies.utas.edu.au.
authors.forename: David H
authors.initials: DH
authors.lastname: Small
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D015536:Down-Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C102938:Neurog2 protein, mouse
keywords: Amyloid Precursor Protein (APP); Basic Helix-loop-helix Transcription Factor (bHLH); Neurogenesis; RNA Interference (RNAi); Transgenic Mice