Ciliogenesis and cell cycle alterations contribute to KIF2A-related malformations of cortical development.

[en] 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.

Disciplines :

Neurology

Author, co-author :

Broix, Loic

Asselin, Laure

Gomes Da Silva, Carla ; Université de Liège > GIGA - Neurosciences

Ivanova, Ekaterina L.

Tilly, Peggy

Gilet, Johan G.

Lebrun, Nicolas

Jagline, Helene

Muraca, Giuseppe

Saillour, Yoann

More authors (10 more)

Language :

English

Title :

Ciliogenesis and cell cycle alterations contribute to KIF2A-related malformations of cortical development.

Publication date :

2018

Journal title :

Human Molecular Genetics

ISSN :

0964-6906

eISSN :

1460-2083

Publisher :

Oxford University Press, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 04 January 2018

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