title: Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain.
abstract: Altered microRNA profiles have been implicated in human brain disorders. However, the functional contribution of individual microRNAs to neuronal development and function is largely unknown. Here, we report biological functions for miR-19 in adult neurogenesis. We determined that miR-19 is enriched in neural progenitor cells (NPCs) and downregulated during neuronal development in the adult hippocampus. By manipulating miR-19 in NPCs for gain- and loss-of-function studies, we discovered that miR-19 regulates cell migration by directly targeting Rapgef2. Concordantly, dysregulation of miR-19 in NPCs alters the positioning of newborn neurons in the adult brain. Furthermore, we found abnormal expression of miR-19 in human NPCs generated from schizophrenic patient-derived induced pluripotent stem cells (iPSCs) that have been described as displaying aberrant migration. Our study demonstrates the significance of posttranscriptional gene regulation by miR-19 in preventing the irregular migration of adult-born neurons that may contribute to the etiology of schizophrenia.
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: jhan@salk.edu.
authors.forename: Jinju
authors.initials: J
authors.lastname: Han
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Institute of Physiology, University of Greifswald, 17495 Karlsburg, Germany.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Schafer
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Apua
authors.initials: A
authors.lastname: Paquola
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Clemenson
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Toda
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jinseo
authors.initials: J
authors.lastname: Oh
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Aimee R
authors.initials: AR
authors.lastname: Pankonin
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Bo Suk
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Johnston
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Anindita
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Ahmet M
authors.initials: AM
authors.lastname: Denli
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: gage@salk.edu.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000328:Adult; D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D007231:Infant, Newborn; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology
chemical_list: C549214:MIRN19A microRNA, human; C561642:MIRN19 microRNA, mouse; D035683:MicroRNAs
keywords: Rapgef2; adult neurogenesis; cell migration; hippocampus; human induced pluripotent stem cells (iPSCs); miR-19; microRNA (miRNA); microRNA in vivo functions; neural progenitor cells (NPCs); polycistronic microRNAs; schizophrenia