title: An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals.
abstract: Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain.
authors.affiliation: Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.|Brain/Liver Interface Medicine Research Center, Kanazawa University, Ishikawa 920-8640, Japan.|Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Toda
authors.affiliation: Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.|Brain/Liver Interface Medicine Research Center, Kanazawa University, Ishikawa 920-8640, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shinmyo
authors.affiliation: Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.|Brain/Liver Interface Medicine Research Center, Kanazawa University, Ishikawa 920-8640, Japan.
authors.forename: Tung Anh
authors.initials: TA
authors.lastname: Dinh Duong
authors.affiliation: Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.|Brain/Liver Interface Medicine Research Center, Kanazawa University, Ishikawa 920-8640, Japan.|Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.|Brain/Liver Interface Medicine Research Center, Kanazawa University, Ishikawa 920-8640, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000254:growth & development*; D005289:Ferrets; D020547:Lateral Ventricles / Q000254:growth & development*; D055495:Neurogenesis; D013234:Stem Cells / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000502:physiology
chemical_list: D020825:T-Box Domain Proteins