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Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer
Granule neurons are the most common cell type in the cerebellum. They are generated in the external granule layer and migrate inwardly, forming the internal granule layer. Small Rho GTPases play various roles during development of the nervous system and may be involved in generation, differentiation...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436960/ https://www.ncbi.nlm.nih.gov/pubmed/36050459 http://dx.doi.org/10.1038/s41598-022-19252-y |
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author | Katayama, Kei-ichi Zheng, Yi Inoue, Norimitsu |
author_facet | Katayama, Kei-ichi Zheng, Yi Inoue, Norimitsu |
author_sort | Katayama, Kei-ichi |
collection | PubMed |
description | Granule neurons are the most common cell type in the cerebellum. They are generated in the external granule layer and migrate inwardly, forming the internal granule layer. Small Rho GTPases play various roles during development of the nervous system and may be involved in generation, differentiation and migration of granule neurons. We deleted Rac1, a member of small Rho GTPases, by GFAP-Cre driver in cerebellar granule neurons and Bergmann glial cells. Rac1(flox/flox); Cre mice showed impaired migration and slight reduction in the number of granule neurons in the internal granule layer. Deletion of both Rac1 and Rac3 resulted in almost complete absence of granule neurons. Rac-deficient granule neurons differentiated into p27 and NeuN-expressing post mitotic neurons, but died before migration to the internal granule layer. Loss of Rac3 has little effect on granule neuron development. Rac1(flox/flox); Rac3(+/−); Cre mice showed intermediate phenotype between Rac1(flox/flox); Cre and Rac1(flox/flox); Rac3(−/−); Cre mice in both survival and migration of granule neurons. Rac3 itself seems to be unimportant in the development of the cerebellum, but has some roles in Rac1-deleted granule neurons. Conversely, overall morphology of Rac1(+/flox); Rac3(−/−); Cre cerebella was normal. One allele of Rac1 is therefore thought to be sufficient to promote development of cerebellar granule neurons. |
format | Online Article Text |
id | pubmed-9436960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94369602022-09-03 Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer Katayama, Kei-ichi Zheng, Yi Inoue, Norimitsu Sci Rep Article Granule neurons are the most common cell type in the cerebellum. They are generated in the external granule layer and migrate inwardly, forming the internal granule layer. Small Rho GTPases play various roles during development of the nervous system and may be involved in generation, differentiation and migration of granule neurons. We deleted Rac1, a member of small Rho GTPases, by GFAP-Cre driver in cerebellar granule neurons and Bergmann glial cells. Rac1(flox/flox); Cre mice showed impaired migration and slight reduction in the number of granule neurons in the internal granule layer. Deletion of both Rac1 and Rac3 resulted in almost complete absence of granule neurons. Rac-deficient granule neurons differentiated into p27 and NeuN-expressing post mitotic neurons, but died before migration to the internal granule layer. Loss of Rac3 has little effect on granule neuron development. Rac1(flox/flox); Rac3(+/−); Cre mice showed intermediate phenotype between Rac1(flox/flox); Cre and Rac1(flox/flox); Rac3(−/−); Cre mice in both survival and migration of granule neurons. Rac3 itself seems to be unimportant in the development of the cerebellum, but has some roles in Rac1-deleted granule neurons. Conversely, overall morphology of Rac1(+/flox); Rac3(−/−); Cre cerebella was normal. One allele of Rac1 is therefore thought to be sufficient to promote development of cerebellar granule neurons. Nature Publishing Group UK 2022-09-01 /pmc/articles/PMC9436960/ /pubmed/36050459 http://dx.doi.org/10.1038/s41598-022-19252-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Article Katayama, Kei-ichi Zheng, Yi Inoue, Norimitsu Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
title | Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
title_full | Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
title_fullStr | Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
title_full_unstemmed | Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
title_short | Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
title_sort | rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436960/ https://www.ncbi.nlm.nih.gov/pubmed/36050459 http://dx.doi.org/10.1038/s41598-022-19252-y |
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