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TCF7L2 regulates postmitotic differentiation programmes and excitability patterns in the thalamus.
Lipiec, Marcin Andrzej; Bem, Joanna; Kozinski, Kamil; Chakraborty, Chaitali; Urban-Ciecko, Joanna; Zajkowski, Tomasz; Dabrowski, Michal; Szewczyk, Lukasz Mateusz; Toval, Angel; Ferran, José Luis; Nagalski, Andrzej; Wisniewska, Marta Barbara.
Afiliação
  • Lipiec MA; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
  • Bem J; Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
  • Kozinski K; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
  • Chakraborty C; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
  • Urban-Ciecko J; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
  • Zajkowski T; Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland.
  • Dabrowski M; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
  • Szewczyk LM; Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland.
  • Toval A; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
  • Ferran JL; Department of Human Anatomy and Psychobiology, School of Medicine, University of Murcia and IMIB-Arrixaca Institute, Campus de la Salud, 30120 El Palmar, Murcia, Spain.
  • Nagalski A; Department of Human Anatomy and Psychobiology, School of Medicine, University of Murcia and IMIB-Arrixaca Institute, Campus de la Salud, 30120 El Palmar, Murcia, Spain.
  • Wisniewska MB; Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
Development ; 147(16)2020 08 25.
Article em En | MEDLINE | ID: mdl-32675279
ABSTRACT
Neuronal phenotypes are controlled by terminal selector transcription factors in invertebrates, but only a few examples of such regulators have been provided in vertebrates. We hypothesised that TCF7L2 regulates different stages of postmitotic differentiation in the thalamus, and functions as a thalamic terminal selector. To investigate this hypothesis, we used complete and conditional knockouts of Tcf7l2 in mice. The connectivity and clustering of neurons were disrupted in the thalamo-habenular region in Tcf7l2-/- embryos. The expression of subregional thalamic and habenular transcription factors was lost and region-specific cell migration and axon guidance genes were downregulated. In mice with a postnatal Tcf7l2 knockout, the induction of genes that confer thalamic terminal electrophysiological features was impaired. Many of these genes proved to be direct targets of TCF7L2. The role of TCF7L2 in terminal selection was functionally confirmed by impaired firing modes in thalamic neurons in the mutant mice. These data corroborate the existence of master regulators in the vertebrate brain that control stage-specific genetic programmes and regional subroutines, maintain regional transcriptional network during embryonic development, and induce terminal selection postnatally.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tálamo / Diferenciação Celular / Transmissão Sináptica / Regulação da Expressão Gênica no Desenvolvimento / Fator de Transcrição 4 / Mitose Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tálamo / Diferenciação Celular / Transmissão Sináptica / Regulação da Expressão Gênica no Desenvolvimento / Fator de Transcrição 4 / Mitose Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article