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@ARTICLE{Zaidi:293600,
author = {D. Zaidi and K. Chinnappa and B. N. Yigit and V. Viola and
C. Cifuentes-Diaz and A. Jabali$^*$ and A. Uzquiano and E.
Lemesre and F. Perez and J. Ladewig$^*$ and J. Ferent and N.
Ozlu and F. Francis},
title = {{F}orebrain {E}ml1 depletion reveals early centrosomal
dysfunction causing subcortical heterotopia.},
journal = {The journal of cell biology},
volume = {223},
number = {12},
issn = {0021-9525},
address = {New York, NY},
publisher = {Rockefeller Univ. Press},
reportid = {DKFZ-2024-01917},
pages = {e202310157},
year = {2024},
abstract = {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.},
keywords = {Animals / Centrosome: metabolism / Humans /
Microtubule-Associated Proteins: genetics /
Microtubule-Associated Proteins: metabolism /
Prosencephalon: metabolism / Prosencephalon: pathology /
Prosencephalon: embryology / Microtubules: metabolism / Mice
/ Cilia: metabolism / Cilia: pathology / Mutation: genetics
/ Ependymoglial Cells: metabolism / Ependymoglial Cells:
pathology / Cell Cycle: genetics / Microtubule-Associated
Proteins (NLM Chemicals) / Eml1 protein, mouse (NLM
Chemicals) / Eml1 protein, human (NLM Chemicals)},
cin = {A340},
ddc = {570},
cid = {I:(DE-He78)A340-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39316454},
doi = {10.1083/jcb.202310157},
url = {https://inrepo02.dkfz.de/record/293600},
}