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An early cell shape transition drives evolutionary expansion of the human forebrain.
Benito-Kwiecinski, Silvia; Giandomenico, Stefano L; Sutcliffe, Magdalena; Riis, Erlend S; Freire-Pritchett, Paula; Kelava, Iva; Wunderlich, Stephanie; Martin, Ulrich; Wray, Gregory A; McDole, Kate; Lancaster, Madeline A.
Afiliação
  • Benito-Kwiecinski S; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • Giandomenico SL; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • Sutcliffe M; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • Riis ES; Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA, UK.
  • Freire-Pritchett P; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • Kelava I; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • Wunderlich S; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), REBIRTH-Research Center for Translational and Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Member of the German Center for
  • Martin U; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), REBIRTH-Research Center for Translational and Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Member of the German Center for
  • Wray GA; Department of Biology, Duke University, Biological Sciences Building, 124 Science Drive, Durham, NC 27708, USA.
  • McDole K; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • Lancaster MA; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: madeline.lancaster@mrc-lmb.cam.ac.uk.
Cell ; 184(8): 2084-2102.e19, 2021 04 15.
Article em En | MEDLINE | ID: mdl-33765444
The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla, and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that neuroepithelial differentiation is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition, associated with differences in interkinetic nuclear migration and cell cycle length. Comparative RNA sequencing (RNA-seq) reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2, a known epithelial-mesenchymal transition regulator. We show that ZEB2 promotes neuroepithelial transition, and its manipulation and downstream signaling leads to acquisition of nonhuman ape architecture in the human context and vice versa, establishing an important role for neuroepithelial cell shape in human brain expansion.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Forma Celular / Evolução Biológica Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Forma Celular / Evolução Biológica Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article