title: The effect of variation in expression of the candidate dyslexia susceptibility gene homolog Kiaa0319 on neuronal migration and dendritic morphology in the rat.
abstract: We investigated the postnatal effects of embryonic knockdown and overexpression of the candidate dyslexia gene homolog Kiaa0319. We used in utero electroporation to transfect cells in E15/16 rat neocortical ventricular zone with either 1) small hairpin RNA (shRNA) vectors targeting Kiaa0319, 2) a KIAA0319 expression construct, 3) Kiaa0319 shRNA along with KIAA0319 expression construct ("rescue"), or 4) a scrambled version of Kiaa0319 shRNA. Knockdown, but not overexpression, of Kiaa0319 resulted in periventricular heterotopias that contained large numbers of both transfected and non-transfected neurons. This suggested that Kiaa0319 shRNA disrupts neuronal migration by cell autonomous as well as non-cell autonomous mechanisms. Of the Kiaa0319 shRNA-transfected neurons that migrated into the cortical plate, most migrated to their appropriate lamina. In contrast, neurons transfected with the KIAA0319 expression vector attained laminar positions subjacent to their expected positions. Neurons transfected with Kiaa0319 shRNA exhibited apical, but not basal, dendrite hypertrophy, which was rescued by overexpression of KIAA0319. The results provide additional supportive evidence linking candidate dyslexia susceptibility genes to migrational disturbances during brain development, and extends the role of Kiaa0319 to include growth and differentiation of dendrites.
authors.affiliation: The Dyslexia Research Laboratory, Division of Behavioral Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Peschansky
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Burbridge
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Volz
authors.forename: Christopher
authors.initials: C
authors.lastname: Fiondella
authors.forename: Zach
authors.initials: Z
authors.lastname: Wissner-Gross
authors.forename: Albert M
authors.initials: AM
authors.lastname: Galaburda
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lo Turco
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Rosen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D003712:Dendrites; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C080632:CUX1 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C500377:KIAA0319 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D001973:Bromodeoxyuridine
references.citation: Semin Fetal Neonatal Med. 2006 Dec;11(6):489-97
references.pmid: 16962837
references.citation: J Neurosci. 2000 Apr 1;20(7):2439-50
references.pmid: 10729324
references.citation: Pediatr Neurol. 1991 Jul-Aug;7(4):275-80
references.pmid: 1718291
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17053-8
references.pmid: 16278297
references.citation: J Comp Neurol. 2000 Mar 20;418(4):423-40
references.pmid: 10713571
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11553-8
references.pmid: 12954984
references.citation: Neuron. 2004 Jan 22;41(2):175-7
references.pmid: 14741096
references.citation: Childs Nerv Syst. 1999 Sep;15(9):444-8; discussion 449-50
references.pmid: 10502002
references.citation: Curr Biol. 2002 Jul 23;12(14):1233-9
references.pmid: 12176334
references.citation: Neuroreport. 2000 Jul 14;11(10):2185-9
references.pmid: 10923667
references.citation: Neuroscience. 2006 Dec 1;143(2):515-22
references.pmid: 16989952
references.citation: Ann Neurol. 1985 Aug;18(2):222-33
references.pmid: 4037763
references.citation: Rev Neurol. 1997 May;25(141):673-82
references.pmid: 9206590
references.citation: Biol Psychiatry. 2007 Oct 1;62(7):811-7
references.pmid: 17597587
references.citation: Cereb Cortex. 2009 Apr;19(4):861-75
references.pmid: 18701438
references.citation: Neuron. 2004 Jan 22;41(2):203-13
references.pmid: 14741102
references.citation: Genes Brain Behav. 2007 Oct;6(7):640-6
references.pmid: 17309662
references.citation: Cell. 1998 Jan 9;92(1):51-61
references.pmid: 9489699
references.citation: Biochem J. 2004 Jul 15;381(Pt 2):471-81
references.pmid: 15099191
references.citation: Neuroscience. 2008 Mar 27;152(3):723-33
references.pmid: 18313856
references.citation: Am J Hum Genet. 2004 Dec;75(6):1046-58
references.pmid: 15514892
references.citation: Nat Neurosci. 2003 Dec;6(12):1277-83
references.pmid: 14625554
references.citation: Nat Rev Neurosci. 2007 Jun;8(6):427-37
references.pmid: 17514196
references.citation: Cell Cycle. 2004 Jun;3(6):747-51
references.pmid: 15118415
references.citation: J Comp Neurol. 2001 Apr 23;433(1):101-14
references.pmid: 11283952
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):556-60
references.pmid: 17450541
references.citation: Ann Neurol. 1990 Dec;28(6):727-38
references.pmid: 2285260
references.citation: Neurology. 2005 Mar 8;64(5):799-803
references.pmid: 15753412
references.citation: J Am Soc Nephrol. 2001 Apr;12(4):834-845
references.pmid: 11274246
references.citation: Hum Mol Genet. 2006 May 15;15(10):1659-66
references.pmid: 16600991
references.citation: Am J Psychiatry. 2008 Dec;165(12):1576-84
references.pmid: 18829873
references.citation: Neuroscience. 2003;119(1):43-52
references.pmid: 12763067
references.citation: Cereb Cortex. 2007 Nov;17(11):2562-72
references.pmid: 17218481
references.citation: Cell. 2007 Jan 12;128(1):45-57
references.pmid: 17218254
references.citation: Hum Mol Genet. 2008 Mar 15;17(6):859-71
references.pmid: 18063668
references.citation: Cereb Cortex. 2004 May;14(5):586-93
references.pmid: 15054074
references.citation: Dev Biol. 2008 Jan 15;313(2):648-58
references.pmid: 18054781
references.citation: Brain Res Dev Brain Res. 1994 Oct 14;82(1-2):127-35
references.pmid: 7842500
references.citation: Genomics. 1998 Sep 1;52(2):214-8
references.pmid: 9782089
references.citation: PLoS Genet. 2005 Oct;1(4):e50
references.pmid: 16254601
references.citation: Am J Hum Genet. 2005 Apr;76(4):581-91
references.pmid: 15717286
references.citation: Cereb Cortex. 2000 Oct;10(10):1005-13
references.pmid: 11007551
references.citation: Neurology. 2006 Jan 24;66(2):294; author reply 294
references.pmid: 16434687
references.citation: Neuron. 2004 Apr 22;42(2):213-23
references.pmid: 15091338
references.citation: Neuron. 2006 May 4;50(3):377-88
references.pmid: 16675393
references.citation: Mol Psychiatry. 2006 Dec;11(12):1085-91, 1061
references.pmid: 17033633
references.citation: J Comp Neurol. 2004 Nov 8;479(2):168-80
references.pmid: 15452856
references.citation: Trends Cogn Sci. 2006 Jun;10(6):250-7
references.pmid: 16675285
references.citation: Radiographics. 2005 Jan-Feb;25(1):53-65; discussion 66-8
references.pmid: 15653586
references.citation: Development. 2001 Feb;128(3):353-63
references.pmid: 11152634
references.citation: Am J Hum Genet. 2006 Jan;78(1):52-62
references.pmid: 16385449
references.citation: Neuron. 1999 Jun;23(2):257-71
references.pmid: 10399933
references.citation: Ann Neurol. 1979 Aug;6(2):94-100
references.pmid: 496415