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Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.
Barão, Soraia; Xu, Yijun; Llongueras, José P; Vistein, Rachel; Goff, Loyal; Nielsen, Kristina J; Bae, Byoung-Il; Smith, Richard S; Walsh, Christopher A; Stein-O'Brien, Genevieve; Müller, Ulrich.
Afiliación
  • Barão S; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. sbarao@jhmi.edu.
  • Xu Y; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Llongueras JP; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Vistein R; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Goff L; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Nielsen KJ; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Bae BI; Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, 06032, USA.
  • Smith RS; Northwestern University, Feinberg School of Medicine, Department of Pharmacology, Chicago, IL, 60611, USA.
  • Walsh CA; Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Stein-O'Brien G; Howard Hughes Medical Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Müller U; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Nat Commun ; 15(1): 8043, 2024 Sep 14.
Article en En | MEDLINE | ID: mdl-39271675
ABSTRACT
The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown. Here we show that the transcription factors BRN1 and BRN2 have an evolutionary conserved function in neocortical progenitors to control their proliferative capacity and the switch from direct to indirect neurogenesis. Functional studies in mice and ferrets show that BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulate progenitor behavior. Analysis of transcriptomics data from genetically modified macaques provides evidence that these molecular pathways are conserved in non-human primates. Our findings thus demonstrate that BRN1/2 are central regulators of gene expression programs in neocortical progenitors critical to determine brain size during evolution.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación del Desarrollo de la Expresión Génica / Neocórtex / Factores del Dominio POU / Neurogénesis / Células-Madre Neurales Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación del Desarrollo de la Expresión Génica / Neocórtex / Factores del Dominio POU / Neurogénesis / Células-Madre Neurales Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido