Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain

Jinju Han; Hyung Joon Kim; Simon T. Schafer; Apua Paquola; Gregory D. Clemenson; Tomohisa Toda; Jinseo Oh; Aimee R. Pankonin; Bo Suk Lee; Stephen T. Johnston; Anindita Sarkar; Ahmet M. Denli; Fred H. Gage

doi:10.1016/j.neuron.2016.05.034

Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain

Jinju Han, Hyung Joon Kim, Simon T. Schafer, Apua Paquola, Gregory D. Clemenson, Tomohisa Toda, Jinseo Oh, Aimee R. Pankonin, Bo Suk Lee, Stephen T. Johnston, Anindita Sarkar, Ahmet M. Denli, Fred H. Gage

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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.

Original language	English (US)
Pages (from-to)	79-89
Number of pages	11
Journal	Neuron
Volume	91
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2016.05.034
State	Published - Jul 6 2016
Externally published	Yes

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

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2016.05.034

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@article{6d7609a49ad1430fadbdb71b9f0bdd36,

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.",

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",

author = "Jinju Han and Kim, {Hyung Joon} and Schafer, {Simon T.} and Apua Paquola and Clemenson, {Gregory D.} and Tomohisa Toda and Jinseo Oh and Pankonin, {Aimee R.} and Lee, {Bo Suk} and Johnston, {Stephen T.} and Anindita Sarkar and Denli, {Ahmet M.} and Gage, {Fred H.}",

note = "Funding Information: This work was supported by the Life Science Research Foundation (J.H.), California Institute for Regenerative Medicine Training Grant (H.J.K. and A.S.), the McDonnell Foundation (H.J.K.), the Helmsley Foundation, the JPB Foundation, the Engman Foundation, and the Mathers Foundation. We are grateful to Drs. L. Naldini and L. He for providing plasmids, Dr. Y.K. Kim for discussion and critical reading of this manuscript, and current and previous members of F.H.G.{\textquoteright}s lab for helpful discussions. We also thank M.L. Gage for editorial comments and E. Mejia for technical help. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = jul,

day = "6",

doi = "10.1016/j.neuron.2016.05.034",

language = "English (US)",

volume = "91",

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T1 - Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain

AU - Han, Jinju

AU - Kim, Hyung Joon

AU - Schafer, Simon T.

AU - Paquola, Apua

AU - Clemenson, Gregory D.

AU - Toda, Tomohisa

AU - Oh, Jinseo

AU - Pankonin, Aimee R.

AU - Lee, Bo Suk

AU - Johnston, Stephen T.

AU - Sarkar, Anindita

AU - Denli, Ahmet M.

AU - Gage, Fred H.

N1 - Funding Information: This work was supported by the Life Science Research Foundation (J.H.), California Institute for Regenerative Medicine Training Grant (H.J.K. and A.S.), the McDonnell Foundation (H.J.K.), the Helmsley Foundation, the JPB Foundation, the Engman Foundation, and the Mathers Foundation. We are grateful to Drs. L. Naldini and L. He for providing plasmids, Dr. Y.K. Kim for discussion and critical reading of this manuscript, and current and previous members of F.H.G.’s lab for helpful discussions. We also thank M.L. Gage for editorial comments and E. Mejia for technical help. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/7/6

Y1 - 2016/7/6

N2 - 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.

AB - 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.

KW - Rapgef2

KW - adult neurogenesis

KW - cell migration

KW - hippocampus

KW - human induced pluripotent stem cells (iPSCs)

KW - miR-19

KW - microRNA (miRNA)

KW - microRNA in vivo functions

KW - neural progenitor cells (NPCs)

KW - polycistronic microRNAs

KW - schizophrenia

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AN - SCOPUS:84991230137

SN - 0896-6273

VL - 91

SP - 79

EP - 89

JO - Neuron

JF - Neuron

IS - 1

ER -

Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain

Abstract

Keywords

ASJC Scopus subject areas

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