Jinju Han1,*, Hyung Joon Kim1, Simon T. Schafer1, 2, Apua Paquola1, Gregory D. Clemenson1, Tomohisa Toda1, Jinseo Oh1, Aimee R. Pankonin1, Bo Suk Lee1, Stephen T. Johnston1, Anindita Sarkar1, Ahmet M. Denli1, Fred H. Gage1,*
1 Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
2 Institute of Physiology, University of Greifswald, 17495 Karlsburg, Germany
*Corresponding author : Fred H. Gage, Jinju Han
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 : miR-19; microRNA (miRNA); polycistronic microRNAs; microRNA in vivo functions; Rapgef2; cell migration; neural progenitor cells (NPCs); adult neurogenesis; hippocampus; schizophrenia; human induced pluripotent stem cells (iPSCs)