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Cell migration is impaired in XPA‐deficient cells

Xeroderma pigmentosum (XP) is a hereditary disorder characterized by photosensitivity, predisposition to skin cancers, and neurological abnormalities including microcephaly and progressive neurodegeneration. A lack of nucleotide excision repair (NER) in patients with XP can cause hypersensitivity to...

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Autores principales: Takeuchi, Seiji, Fukumoto, Takeshi, Takemori, Chihiro, Saito, Naoaki, Nishigori, Chikako, Sato, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927838/
https://www.ncbi.nlm.nih.gov/pubmed/36816512
http://dx.doi.org/10.1096/fba.2022-00084
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author Takeuchi, Seiji
Fukumoto, Takeshi
Takemori, Chihiro
Saito, Naoaki
Nishigori, Chikako
Sato, Makoto
author_facet Takeuchi, Seiji
Fukumoto, Takeshi
Takemori, Chihiro
Saito, Naoaki
Nishigori, Chikako
Sato, Makoto
author_sort Takeuchi, Seiji
collection PubMed
description Xeroderma pigmentosum (XP) is a hereditary disorder characterized by photosensitivity, predisposition to skin cancers, and neurological abnormalities including microcephaly and progressive neurodegeneration. A lack of nucleotide excision repair (NER) in patients with XP can cause hypersensitivity to the sun, leading to skin cancer, whereas the etiology of the neuronal symptoms of XP remains ambiguous. There are various neurological disorders that perturb neuronal migration, causing mislocalization and disorganization of the cortical lamination. Here, we investigated the role of the XP group‐A (Xpa) gene in directed cell migration. First, we adopted an in utero electroporation method to transduce shRNA vectors into the murine embryonic cerebral cortex for the in vivo knockdown of Xpa. Xpa‐knockdown neurons in the embryonic cerebral cortex showed abnormal cell migration, cell cycle exit, and differentiation. The genotype–phenotype relationship between the lack of XPA and cell migration abnormalities was confirmed using both a scratch assay and time‐lapse microscopy in XP‐A patient‐derived fibroblasts. Unlike healthy cells, these cells showed impairment in overall mobility and the direction of motility. Therefore, abnormal cell migration may explain neural tissue abnormalities in patients with XP‐A.
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spelling pubmed-99278382023-02-16 Cell migration is impaired in XPA‐deficient cells Takeuchi, Seiji Fukumoto, Takeshi Takemori, Chihiro Saito, Naoaki Nishigori, Chikako Sato, Makoto FASEB Bioadv Research Articles Xeroderma pigmentosum (XP) is a hereditary disorder characterized by photosensitivity, predisposition to skin cancers, and neurological abnormalities including microcephaly and progressive neurodegeneration. A lack of nucleotide excision repair (NER) in patients with XP can cause hypersensitivity to the sun, leading to skin cancer, whereas the etiology of the neuronal symptoms of XP remains ambiguous. There are various neurological disorders that perturb neuronal migration, causing mislocalization and disorganization of the cortical lamination. Here, we investigated the role of the XP group‐A (Xpa) gene in directed cell migration. First, we adopted an in utero electroporation method to transduce shRNA vectors into the murine embryonic cerebral cortex for the in vivo knockdown of Xpa. Xpa‐knockdown neurons in the embryonic cerebral cortex showed abnormal cell migration, cell cycle exit, and differentiation. The genotype–phenotype relationship between the lack of XPA and cell migration abnormalities was confirmed using both a scratch assay and time‐lapse microscopy in XP‐A patient‐derived fibroblasts. Unlike healthy cells, these cells showed impairment in overall mobility and the direction of motility. Therefore, abnormal cell migration may explain neural tissue abnormalities in patients with XP‐A. John Wiley and Sons Inc. 2022-12-12 /pmc/articles/PMC9927838/ /pubmed/36816512 http://dx.doi.org/10.1096/fba.2022-00084 Text en © 2022 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Takeuchi, Seiji
Fukumoto, Takeshi
Takemori, Chihiro
Saito, Naoaki
Nishigori, Chikako
Sato, Makoto
Cell migration is impaired in XPA‐deficient cells
title Cell migration is impaired in XPA‐deficient cells
title_full Cell migration is impaired in XPA‐deficient cells
title_fullStr Cell migration is impaired in XPA‐deficient cells
title_full_unstemmed Cell migration is impaired in XPA‐deficient cells
title_short Cell migration is impaired in XPA‐deficient cells
title_sort cell migration is impaired in xpa‐deficient cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927838/
https://www.ncbi.nlm.nih.gov/pubmed/36816512
http://dx.doi.org/10.1096/fba.2022-00084
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