title: Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis.
abstract: The timing of cortical neurogenesis has a major effect on the size and organization of the mature cortex. The deletion of the LIM-homeodomain transcription factor Lhx2 in cortical progenitors by Nestin-cre leads to a dramatically smaller cortex. Here we report that Lhx2 regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis. The loss of Lhx2 in cortical progenitors results in precocious radial glia differentiation and a temporal shift of cortical neurogenesis. We further investigated the underlying mechanisms at play and demonstrated that in the absence of Lhx2, the Wnt/β-catenin pathway failed to maintain progenitor proliferation. We developed and applied a mathematical model that reveals how precocious neurogenesis affected cortical surface and thickness. Thus, we concluded that Lhx2 is required for β-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan; Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 114, Taiwan;
authors.forename: Lea Chia-Ling
authors.initials: LC
authors.lastname: Hsu
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan;
authors.forename: Sean
authors.initials: S
authors.lastname: Nam
authors.affiliation: Collège de France, Centre for Interdisciplinary Research in Biology, CNRS UMR 7241, INSERM U1050, MemoLife Paris Science Lettres, 75231 Paris, France;
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan;
authors.forename: Ching-Pu
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan;
authors.forename: Chia-Fang
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan;
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Collège de France, Centre for Interdisciplinary Research in Biology, CNRS UMR 7241, INSERM U1050, MemoLife Paris Science Lettres, 75231 Paris, France; Inria Paris-Rocquencourt, Mycenae Team, 78153 Le Chesnay, France.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Touboul
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan; Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 114, Taiwan; schou@gate.sinica.edu.tw.
authors.forename: Shen-Ju
authors.initials: SJ
authors.lastname: Chou
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology*; D003198:Computer Simulation; D017931:DNA Primers / Q000235:genetics; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D007211:Indoles; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005697:Galactosides; D007211:Indoles; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors; D051176:beta Catenin; D008156:Luciferases; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
keywords: Lhx2; cortical neurogenesis; β-catenin