title: Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate.
abstract: Evolution of the mammalian brain encompassed a remarkable increase in size of the cerebral cortex, which includes tangential and radial expansion. However, the mechanisms underlying these key features are still largely unknown. Here, we identified the DNA-associated protein Trnp1 as a regulator of cerebral cortex expansion in both of these dimensions. Gain- and loss-of-function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion. In contrast, lower levels promote radial expansion, with a potent increase of the number of intermediate progenitors and basal radial glial cells leading to folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences in the cerebral cortex of human fetuses, anticipating radial or tangential expansion. Thus, the dynamic regulation of Trnp1 is critical to control tangential and radial expansion of the cerebral cortex in mammals.
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilian University Munich, Munich, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Stahl
authors.forename: Tessa
authors.initials: T
authors.lastname: Walcher
authors.forename: Camino
authors.initials: C
authors.lastname: De Juan Romero
authors.forename: Gregor Alexander
authors.initials: GA
authors.lastname: Pilz
authors.forename: Silvia
authors.initials: S
authors.lastname: Cappello
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sanz-Aquela
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
authors.forename: Víctor
authors.initials: V
authors.lastname: Borrell
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development*; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C581865:Trnp1 protein, human; C581864:Trnp1 protein, mouse