title: Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex.
abstract: Amyloid precursor protein (APP) is a transmembrane glycoprotein proteolytically processed to release amyloid beta, a pathological hallmark of Alzheimer's disease. APP is expressed throughout the developing and mature brain; however, the primary function of this protein is unknown. We previously demonstrated that APP deficiency enhances neurogenesis, but the mechanisms underlying this process are not known. Here we show that APP regulates the expression of microRNAs in the cortex and in neural progenitors, specifically repressing miR-574-5p. We also show that overexpression of miR-574-5p promotes neurogenesis, but reduces the neural progenitor pool. In contrast, the reduced expression of miR-574-5p inhibits neurogenesis and stimulates proliferation in vitro and in utero. We further demonstrate that the inhibition of miR-574-5p in APP-knockout mice rescues the phenotypes associated with APP deficiency in neurogenesis. Taken together, these results reveal a mechanism in which APP regulates the neurogenesis through miRNA-mediated post-transcriptional regulation.
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.
authors.forename: Selvaratnam
authors.initials: S
authors.lastname: Thevapriya
authors.affiliation: Molecular Neurophysiology Laboratory, Neuroscience & Behavioral Disorders program, DUKE-NUS GMS, Singapore 169857, Singapore.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kim
authors.affiliation: 1] Research Department, National Neuroscience Institute, Singapore 308433, Singapore [2] Animal Gene Editing Laboratory, Biological resource Centre, A*STAR, Singapore 138673, Singapore.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Yu
authors.affiliation: 1] Molecular Neurophysiology Laboratory, Neuroscience & Behavioral Disorders program, DUKE-NUS GMS, Singapore 169857, Singapore [2] Department of Physiology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: H Shawn
authors.initials: HS
authors.lastname: Je
authors.affiliation: 1] Research Department, National Neuroscience Institute, Singapore 308433, Singapore [2] Department of Neurology, National Neuroscience Institute, Singapore 308433, Singapore [3] Neuroscience & Behavioral Disorders program, DUKE-NUS GMS, Singapore 169857, Singapore.
authors.forename: Eng King
authors.initials: EK
authors.lastname: Tan
authors.affiliation: 1] Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore 308433, Singapore [2] Neuroscience & Behavioral Disorders program, DUKE-NUS GMS, Singapore 169857, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis
chemical_list: D016564:Amyloid beta-Protein Precursor; C580862:MIRN574 microRNA, mouse; D035683:MicroRNAs