Xavier Hubert Jaglin

Publications (3)35.53 Total impact

• Source

  Available from: Karine Poirier

  Article: Mutations in the β-Tubulin Gene TUBB5 Cause Microcephaly with Structural Brain Abnormalities.

  Martin Breuss, Julian Ik-Tsen Heng, Karine Poirier, Guoling Tian, Xavier Hubert Jaglin, Zhengdong Qu, Andreas Braun, Thomas Gstrein, Linh Ngo, Matilda Haas, [......], Alain Verloes, Pierre Gressens, Yunli Xie, Kathryn J H Robson, Deepa Selvi Rani, Kumarasamy Thangaraj, Tim Clausen, Jamel Chelly, Nicholas Justin Cowan, David Anthony Keays
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  ABSTRACT: The formation of the mammalian cortex requires the generation, migration, and differentiation of neurons. The vital role that the microtubule cytoskeleton plays in these cellular processes is reflected by the discovery that mutations in various tubulin isotypes cause different neurodevelopmental diseases, including lissencephaly (TUBA1A), polymicrogyria (TUBA1A, TUBB2B, TUBB3), and an ocular motility disorder (TUBB3). Here, we show that Tubb5 is expressed in neurogenic progenitors in the mouse and that its depletion in vivo perturbs the cell cycle of progenitors and alters the position of migrating neurons. We report the occurrence of three microcephalic patients with structural brain abnormalities harboring de novo mutations in TUBB5 (M299V, V353I, and E401K). These mutant proteins, which affect the chaperone-dependent assembly of tubulin heterodimers in different ways, disrupt neurogenic division and/or migration in vivo. Our results provide insight into the functional repertoire of the tubulin gene family, specifically implicating TUBB5 in embryonic neurogenesis and microcephaly.
  Cell reports. 12/2012;
• Article: Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.

  Xavier Hubert Jaglin, Karine Poirier, Yoann Saillour, Emmanuelle Buhler, Guoling Tian, Nadia Bahi-Buisson, Catherine Fallet-Bianco, Françoise Phan-Dinh-Tuy, Xiang Peng Kong, Pascale Bomont, [......], Irina Snoeck, Ghislaine Plessis, Philippe Parent, Cherif Beldjord, Carlos Cardoso, Alfonso Represa, Jonathan Flint, David Anthony Keays, Nicholas Justin Cowan, Jamel Chelly
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  ABSTRACT: Polymicrogyria is a relatively common but poorly understood defect of cortical development characterized by numerous small gyri and a thick disorganized cortical plate lacking normal lamination. Here we report de novo mutations in a beta-tubulin gene, TUBB2B, in four individuals and a 27-gestational-week fetus with bilateral asymmetrical polymicrogyria. Neuropathological examination of the fetus revealed an absence of cortical lamination associated with the presence of ectopic neuronal cells in the white matter and in the leptomeningeal spaces due to breaches in the pial basement membrane. In utero RNAi-based inactivation demonstrates that TUBB2B is required for neuronal migration. We also show that two disease-associated mutations lead to impaired formation of tubulin heterodimers. These observations, together with previous data, show that disruption of microtubule-based processes underlies a large spectrum of neuronal migration disorders that includes not only lissencephaly and pachygyria, but also polymicrogyria malformations.
  Nature Genetics 06/2009; 41(6):746-52. · 35.53 Impact Factor
• Article: Mutations in the β-tubulin gene TUBB2B result in asymmetrical polymicrogyria

  Xavier Hubert Jaglin, Karine Poirier, Yoann Saillour, Emmanuelle Buhler, Guoling Tian, Nadia Bahi-Buisson, Catherine Fallet-Bianco, Françoise Phan Dinh Tuy, Xiang Peng Kong, Pascale Bomont, [......], Irina Snoeck, Ghislaine Plessis, Philippe Parent, Cherif Beldjord, Carlos Cardoso, Alfonso Represa, Jonathan Flint, David Anthony Keays, Nicholas Justin Cowan, Jamel Chelly