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Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene i...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923931/ https://www.ncbi.nlm.nih.gov/pubmed/36782228 http://dx.doi.org/10.1186/s13041-023-01010-4 |
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author | Cheng, Qi Wu, Jing Xia, Yingqian Cheng, Qing Zhao, Yinjuan Zhu, Peixiang Zhang, Wangling Zhang, Shihu Zhang, Lei Yuan, Yushan Li, Chaojun Chen, Guiquan Xue, Bin |
author_facet | Cheng, Qi Wu, Jing Xia, Yingqian Cheng, Qing Zhao, Yinjuan Zhu, Peixiang Zhang, Wangling Zhang, Shihu Zhang, Lei Yuan, Yushan Li, Chaojun Chen, Guiquan Xue, Bin |
author_sort | Cheng, Qi |
collection | PubMed |
description | The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene is inactivated in neural progenitor cells in the developing cerebellum. We report that conditional knockout (cKO) of Ggps1 leads to severe ataxia and deficient locomotion. To identify the underlying mechanisms, we completed a series of cellular and molecular experiments. First, our morphological analysis revealed significantly decreased population of granule cell progenitors (GCPs) and impaired proliferation of GCPs in the developing cerebellum of Ggps1 cKO mice. Second, our molecular analysis showed increased expression of p21, an important cell cycle regulator in Ggps1 cKO mice. Together, this study highlights a critical role of Ggpps-dependent protein prenylation in the proliferation of cerebellar GCPs during cerebellar development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-023-01010-4. |
format | Online Article Text |
id | pubmed-9923931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99239312023-02-14 Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation Cheng, Qi Wu, Jing Xia, Yingqian Cheng, Qing Zhao, Yinjuan Zhu, Peixiang Zhang, Wangling Zhang, Shihu Zhang, Lei Yuan, Yushan Li, Chaojun Chen, Guiquan Xue, Bin Mol Brain Research The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene is inactivated in neural progenitor cells in the developing cerebellum. We report that conditional knockout (cKO) of Ggps1 leads to severe ataxia and deficient locomotion. To identify the underlying mechanisms, we completed a series of cellular and molecular experiments. First, our morphological analysis revealed significantly decreased population of granule cell progenitors (GCPs) and impaired proliferation of GCPs in the developing cerebellum of Ggps1 cKO mice. Second, our molecular analysis showed increased expression of p21, an important cell cycle regulator in Ggps1 cKO mice. Together, this study highlights a critical role of Ggpps-dependent protein prenylation in the proliferation of cerebellar GCPs during cerebellar development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-023-01010-4. BioMed Central 2023-02-13 /pmc/articles/PMC9923931/ /pubmed/36782228 http://dx.doi.org/10.1186/s13041-023-01010-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Cheng, Qi Wu, Jing Xia, Yingqian Cheng, Qing Zhao, Yinjuan Zhu, Peixiang Zhang, Wangling Zhang, Shihu Zhang, Lei Yuan, Yushan Li, Chaojun Chen, Guiquan Xue, Bin Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
title | Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
title_full | Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
title_fullStr | Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
title_full_unstemmed | Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
title_short | Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
title_sort | disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923931/ https://www.ncbi.nlm.nih.gov/pubmed/36782228 http://dx.doi.org/10.1186/s13041-023-01010-4 |
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