title: MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex.
abstract: During the development, tight regulation of the expansion of neural progenitor cells (NPCs) and their differentiation into neurons is crucial for normal cortical formation and function. In this study, we demonstrate that microRNA (miR)-128 regulates the proliferation and differentiation of NPCs by repressing pericentriolar material 1 (PCM1). Specifically, overexpression of miR-128 reduced NPC proliferation but promoted NPC differentiation into neurons both in vivo and in vitro. In contrast, the reduction of endogenous miR-128 elicited the opposite effects. Overexpression of miR-128 suppressed the translation of PCM1, and knockdown of endogenous PCM1 phenocopied the observed effects of miR-128 overexpression. Furthermore, concomitant overexpression of PCM1 and miR-128 in NPCs rescued the phenotype associated with miR-128 overexpression, enhancing neurogenesis but inhibiting proliferation, both in vitro and in utero. Taken together, these results demonstrate a novel mechanism by which miR-128 regulates the proliferation and differentiation of NPCs in the developing neocortex.
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Paul Jong
authors.initials: PJ
authors.lastname: Kim
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore.
authors.forename: Zhongcan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Hidayat
authors.initials: H
authors.lastname: Lokman
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Steven George
authors.initials: SG
authors.lastname: Rozen
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore, Singapore.|Neuroscience and Behavioral Disorders program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Eng King
authors.initials: EK
authors.lastname: Tan
authors.affiliation: Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.|Neuroscience and Behavioral Disorders program, Duke-NUS Graduate Medical School, Singapore, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Hyunsoo Shawn
authors.identifier: http://orcid.org/0000-0002-2924-5621
authors.initials: HS
authors.lastname: Je
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore.|Neuroscience and Behavioral Disorders program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; C550324:Mirn128 microRNA, mouse; C490114:Pcm1 protein, mouse
keywords: developmental biology; miR-128; mouse; neocortex; neurogenesis; neuronal precursor cells; neuroscience; pericentriolar material 1; stem cells