Počet záznamů: 1
TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis
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SYSNO ASEP 0505195 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis Tvůrce(i) Ivanova, E.L. (FR)
Gilet, J.G. (FR)
Sulimenko, Vadym (UMG-J) RID, ORCID
Duchon, A. (FR)
Rudolf, G. (FR)
Runge, K. (FR)
Collins s, S.C. (FR)
Asselin, L. (FR)
Broix, L. (FR)
Drouot, N. (FR)
Tiiiy, P. (FR)
Nusbaum, P. (FR)
Vincent, A. (FR)
Magnant, W. (FR)
Skory, V. (FR)
Birling, M.C. (FR)
Pavlovic, G. (FR)
Godin, J.D. (FR)
Yalcin, B. (FR)
Herault, Y. (FR)
Dráber, Pavel (UMG-J) RID, ORCID
Chelly, J. (FR)
Hinckelmann, M.V. (FR)Celkový počet autorů 23 Číslo článku 2129 Zdroj.dok. Nature Communications. - : Nature Publishing Group
Roč. 10, č. 1 (2019)Poč.str. 18 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova developing mouse-brain ; tubulin small complex ; spindle pole body ; gamma-tubulin ; centrosomal protein ; animal-models ; mutations ; mice ; migration ; gene Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Cell biology CEP GA16-23702S GA ČR - Grantová agentura ČR GA18-27197S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000467702800002 DOI 10.1038/s41467-019-10081-8 Anotace De novo heterozygous missense variants in the gamma-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 Tubg1(Y)(92)(C/+) mouse model and assessed consequences of the mutation. Although centrosomal positioning in bipolar neurons is correct, they fail to initiate locomotion. Furthermore, Tubg1(Y)(92)(C/+) animals show neuroanatomical and behavioral defects and increased epileptic cortical activity. We show that Tubg1(Y)(92)(C/+) mice partially mimic the human phenotype and therefore represent a relevant model for further investigations of the physiopathology of cortical malformations. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2020 Elektronická adresa https://www.nature.com/articles/s41467-019-10081-8
Počet záznamů: 1