Forebrain Eml1 depletion reveals early centrosomal dysfunction causing subcortical heterotopia.

Autor:	Zaidi D; Institut du Fer à Moulin , Paris, France.; Institut National de Santé et de Recherche Médicale (INSERM, UMR-S 1270) , Paris, France.; Sorbonne Université , Paris, France., Chinnappa K; Institut du Fer à Moulin , Paris, France.; Institut National de Santé et de Recherche Médicale (INSERM, UMR-S 1270) , Paris, France.; Sorbonne Université , Paris, France., Yigit BN; Department of Molecular Biology and Genetics, Koc University, İstanbul, Turkiye., Viola V; Institut du Fer à Moulin , Paris, France.; Institut National de Santé et de Recherche Médicale (INSERM, UMR-S 1270) , Paris, France.; Sorbonne Université , Paris, France., Cifuentes-Diaz C; Institut du Fer à Moulin , Paris, France.; Institut National de Santé et de Recherche Médicale (INSERM, UMR-S 1270) , Paris, France.; Sorbonne Université , Paris, France., Jabali A; Central Institute of Mental Health (ZI), Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany.; Hector Institute for Translational Brain Research (HITBR) , Mannheim, Germany.; German Cancer Research Center (DKFZ) , Heidelberg, Germany., Uzquiano A; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, AL, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard , Cambridge, AL, USA., Lemesre E; Dynamics of Intracellular Organization Laboratory, Institut Curie, PSL Research University, Sorbonne Université, Centre National de la Recherche Scientifique, Paris, France., Perez F; Dynamics of Intracellular Organization Laboratory, Institut Curie, PSL Research University, Sorbonne Université, Centre National de la Recherche Scientifique, Paris, France., Ladewig J; Central Institute of Mental Health (ZI), Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany.; Hector Institute for Translational Brain Research (HITBR) , Mannheim, Germany.; German Cancer Research Center (DKFZ) , Heidelberg, Germany., Ferent J; Institut du Fer à Moulin , Paris, France.; Institut National de Santé et de Recherche Médicale (INSERM, UMR-S 1270) , Paris, France.; Sorbonne Université , Paris, France., Ozlu N; Department of Molecular Biology and Genetics, Koc University, İstanbul, Turkiye.; Koc University, Research Center for Translational Medicine (KUTTAM) , İstanbul, Turkiye., Francis F; Institut du Fer à Moulin , Paris, France.; Institut National de Santé et de Recherche Médicale (INSERM, UMR-S 1270) , Paris, France.; Sorbonne Université , Paris, France.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Dec 02; Vol. 223 (12). Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1083/jcb.202310157
Abstrakt:	Subcortical heterotopia is a cortical malformation associated with epilepsy, intellectual disability, and an excessive number of cortical neurons in the white matter. Echinoderm microtubule-associated protein like 1 (EML1) mutations lead to subcortical heterotopia, associated with abnormal radial glia positioning in the cortical wall, prior to malformation onset. This perturbed distribution of proliferative cells is likely to be a critical event for heterotopia formation; however, the underlying mechanisms remain unexplained. This study aimed to decipher the early cellular alterations leading to abnormal radial glia. In a forebrain conditional Eml1 mutant model and human patient cells, primary cilia and centrosomes are altered. Microtubule dynamics and cell cycle kinetics are also abnormal in mouse mutant radial glia. By rescuing microtubule formation in Eml1 mutant embryonic brains, abnormal radial glia delamination and heterotopia volume were significantly reduced. Thus, our new model of subcortical heterotopia reveals the causal link between Eml1's function in microtubule regulation and cell position, both critical for correct cortical development. (© 2024 Zaidi et al.)
Databáze:	MEDLINE
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