> Detailanzeige

Ivanova, Ekaterina L.; Gilet, Johan G.; Sulimenko, Vadym; Duchon, Arnaud; Rudolf, Gabrielle; Runge, Karen; Collins, Stephan C.; Asselin, Laure; Broix, Loic; Drouot, Nathalie; Tilly, Peggy; Nusbaum, Patrick; Vincent, Alexandre; Magnant, William; Skory, Valerie; Birling, Marie-Christine; Pavlovic, Guillaume; Godin, Juliette D.; Yalcin, Binnaz; Hérault, Yann; Dráber, Pavel; Chelly, Jamel; Hinckelmann, Maria-Victoria

TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis
  • Beteiligte: Ivanova, Ekaterina L.; Gilet, Johan G.; Sulimenko, Vadym; Duchon, Arnaud; Rudolf, Gabrielle; Runge, Karen; Collins, Stephan C.; Asselin, Laure; Broix, Loic; Drouot, Nathalie; Tilly, Peggy; Nusbaum, Patrick; Vincent, Alexandre; Magnant, William; Skory, Valerie; Birling, Marie-Christine; Pavlovic, Guillaume; Godin, Juliette D.; Yalcin, Binnaz; Hérault, Yann; Dráber, Pavel; Chelly, Jamel; Hinckelmann, Maria-Victoria
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Nature Communications, 10 (2019) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-019-10081-8
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: AbstractDe novo heterozygous missense variants in the γ-tubulin gene TUBG1 have been linked to human malformations of cortical development associated with intellectual disability and epilepsy. Here, we investigated through in-utero electroporation and in-vivo studies, how four of these variants affect cortical development. We show that TUBG1 mutants affect neuronal positioning, disrupting the locomotion of new-born neurons but without affecting progenitors’ proliferation. We further demonstrate that pathogenic TUBG1 variants are linked to reduced microtubule dynamics but without major structural nor functional centrosome defects in subject-derived fibroblasts. Additionally, we developed a knock-in Tubg1Y92C/+ mouse model and assessed consequences of the mutation. Although centrosomal positioning in bipolar neurons is correct, they fail to initiate locomotion. Furthermore, Tubg1Y92C/+ animals show neuroanatomical and behavioral defects and increased epileptic cortical activity. We show that Tubg1Y92C/+ mice partially mimic the human phenotype and therefore represent a relevant model for further investigations of the physiopathology of cortical malformations.
  • Zugangsstatus: Freier Zugang