title: The newly identified migration inhibitory protein regulates the radial migration in the developing neocortex.
abstract: Neuronal migration is a crucial process in the organization of the developing cerebral cortex. Although a number of positive regulatory mechanisms of radial migration have been identified, negative cell-autonomous mechanisms have yet to be fully described. Here we report a newly identified Migration Inhibitory Protein (MINP, formerly known as 2900011O08Rik) that negatively regulates radial migration. MINP mRNA was specifically detected in the central and peripheral nervous system, and especially enriched in the cerebral cortex. MINP immunoreactivity co-localized with the neuronal marker Tuj1 and was detected in the cytoplasm of post-mitotic neurons. To elucidate the function of MINP in the developing brain, we performed in utero electroporation of MINP siRNA, MINP shRNA, or MINP-overexpressing vectors into mouse cortices and carried out in vivo migration assays. Whereas knockdown of MINP did not alter neuronal morphology, the radial migration was found accelerated by MINP knockdown, and reduced by MINP overexpression. This migration phenotype was also confirmed in vitro, indicating that MINP regulates neuronal migration in a cell-autonomous fashion. Furthermore, downregulation of MINP affected microtubule stability by interacting with tubulin that is a potential mechanism involved in the regulation of neuronal migration.
authors.affiliation: 1] Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan [2] JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Suxiang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: 1] Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan [2] JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: 1] Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan [2] JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan [3] Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0872, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujitani
authors.affiliation: 1] Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan [2] JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D018274:Electroporation; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D019579:Neocortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; C000602221:MINP protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D014404:Tubulin; C462941:beta3 tubulin, mouse
references.citation: Neuron. 1996 Aug;17(2):275-85
references.pmid: 8780651
references.citation: Mol Psychiatry. 2011 Jan;16(1):17-25
references.pmid: 19786961
references.citation: Hum Mutat. 2007 Jul;28(7):674-82
references.pmid: 17480035
references.citation: Trends Neurosci. 2010 Aug;33(8):362-72
references.pmid: 20541813
references.citation: Neuron. 2010 Aug 26;67(4):588-602
references.pmid: 20797536
references.citation: Neuropharmacology. 1993 Nov;32(11):1239-48
references.pmid: 7509049
references.citation: Cell. 2002 Jun 28;109(7):887-900
references.pmid: 12110185
references.citation: Am J Hum Genet. 2011 May 13;88(5):536-47
references.pmid: 21529751
references.citation: J Biol Chem. 2010 Feb 19;285(8):5878-87
references.pmid: 20022952
references.citation: J Cell Sci. 1994 Jun;107 ( Pt 6):1529-43
references.pmid: 7962195
references.citation: Cell. 2009 Sep 4;138(5):990-1004
references.pmid: 19737524
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Oct 1;66(Pt 10):1148-52
references.pmid: 20944204
references.citation: Curr Biol. 2010 Nov 23;20(22):2058-65
references.pmid: 21074438
references.citation: Nat Rev Neurosci. 2002 Jun;3(6):423-32
references.pmid: 12042877
references.citation: Cell. 1998 Jan 9;92(1):51-61
references.pmid: 9489699
references.citation: EMBO J. 2011 Apr 6;30(7):1389-401
references.pmid: 21364532
references.citation: Nat Rev Mol Cell Biol. 2011 Nov 16;12(12):773-86
references.pmid: 22086369
references.citation: Int J Dev Neurosci. 2002 Jun-Aug;20(3-5):349-57
references.pmid: 12175873
references.citation: Cell Stem Cell. 2013 Nov 7;13(5):564-76
references.pmid: 24209760
references.citation: Cell. 2012 Mar 16;148(6):1223-41
references.pmid: 22424231
references.citation: PLoS Biol. 2011 Jan 18;9(1):e1000582
references.pmid: 21267068
references.citation: Nature. 1993 Aug 19;364(6439):717-21
references.pmid: 8355785
references.citation: Nat Neurosci. 2011 Mar;14(3):305-13
references.pmid: 21297631
references.citation: Lancet. 2010 Oct 23;376(9750):1401-8
references.pmid: 20888040
references.citation: Neurochem Res. 2000 Jan;25(1):11-8
references.pmid: 10685599
references.citation: Trends Neurosci. 2000 Aug;23(8):352-9
references.pmid: 10906798
references.citation: J Neurosci. 2011 Jun 22;31(25):9426-39
references.pmid: 21697392
references.citation: Brain. 2010 Jan;133(Pt 1):23-32
references.pmid: 19843651
references.citation: Genes Cells. 2013 Mar;18(3):176-94
references.pmid: 23294285
references.citation: Neuron. 2009 Jul 16;63(1):63-80
references.pmid: 19607793
references.citation: Nat Neurosci. 2008 Jan;11(1):36-44
references.pmid: 18059265
references.citation: Neuron. 1999 Jun;23(2):257-71
references.pmid: 10399933
references.citation: Neuron. 2004 Oct 14;44(2):279-93
references.pmid: 15473967