期刊
HUMAN MOLECULAR GENETICS
卷 27, 期 2, 页码 224-238出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddx384
关键词
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资金
- Strasbourg University
- Agence Nationale de la Recherche [ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002-02]
- Fondation pour la Recherche Medicale (FRM ) [J.C-DEQ20130326477]
- Fondation Maladies Rares
- Fondation NRJ-Institut de France, Agence National de Recherche [ANR 15-CE16-0018-01, E10107KP, ANR-13-BSV-0009-01]
- European Union DESIRE [602531]
- French Agence National de la Recherche [ANR-13-BSV4-0008-01]
- JTC Neurodevelopmental Disorders [NEURON8-Full-815-006 STEM-MCD]
- Inserm
- CNRS
- UPMC
- Fondation Bettencourt Schueller
- Federation pour la Recherche sur le cerveau (FRC)
- Ile de France region
- FRC Rotary
Genetic findings reported by our group and others showed that de novo missense variants in the KIF2A gene underlie malformations of brain development called pachygyria and microcephaly. Though KIF2A is known as member of the Kinesin-13 family involved in the regulation of microtubule end dynamics through its ATP dependent MT-depolymerase activity, how KIF2A variants lead to brain malformations is still largely unknown. Using cellular and in utero electroporation approaches, we show here that KIF2A disease-causing variants disrupts projection neuron positioning and interneuron migration, as well as progenitors proliferation. Interestingly, further dissection of this latter process revealed that ciliogenesis regulation is also altered during progenitors cell cycle. Altogether, our data suggest that deregulation of the coupling between ciliogenesis and cell cycle might contribute to the pathogenesis of KIF2A-related brain malformations. They also raise the issue whether ciliogenesis defects are a hallmark of other brain malformations, such as those related to tubulins and MT-motor proteins variants.
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