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Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control
Minichromosome maintenance protein 5 (MCM5) is a critical cell cycle regulator; its role in DNA replication is well known, but whether it is involved in the regulation of organogenesis in a cell cycle-independent way, is far from clear. In this study, we found that a loss of mcm5 function resulted i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961633/ https://www.ncbi.nlm.nih.gov/pubmed/35204787 http://dx.doi.org/10.3390/biom12020286 |
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author | Zhang, Yu Xia, Jiamin Liu, Min Chen, Bingyu Yang, Min Yu, Xiaoping Ou, Yu Li, Shurong Liu, Xindong Feng, Yi Su, Bingyin Huang, Sizhou |
author_facet | Zhang, Yu Xia, Jiamin Liu, Min Chen, Bingyu Yang, Min Yu, Xiaoping Ou, Yu Li, Shurong Liu, Xindong Feng, Yi Su, Bingyin Huang, Sizhou |
author_sort | Zhang, Yu |
collection | PubMed |
description | Minichromosome maintenance protein 5 (MCM5) is a critical cell cycle regulator; its role in DNA replication is well known, but whether it is involved in the regulation of organogenesis in a cell cycle-independent way, is far from clear. In this study, we found that a loss of mcm5 function resulted in a mildly smaller liver, but that mcm5 overexpression led to liver bifida. Further, the data showed that mcm5 overexpression delayed endodermal migration in the ventral–dorsal axis and induced the liver bifida. Cell cycle analysis showed that a loss of mcm5 function, but not overexpression, resulted in cell cycle delay and increased cell apoptosis during gastrulation, implying that liver bifida was not the result of a cell cycle defect. In terms of its mechanism, our data proves that mcm5 represses the expression of cxcr4a, which sequentially causes a decrease in the expression of itgb1b during gastrulation. The downregulation of the cxcr4a-itgb1b cascade leads to an endodermal migration delay during gastrulation, as well as to the subsequent liver bifida during liver morphogenesis. In conclusion, our results suggest that in a cell cycle-independent way, mcm5 works as a gene expression regulator, either partially and directly, or indirectly repressing the expression of cxcr4a and the downstream gene itgb1b, to coordinate endodermal migration during gastrulation and liver location during liver organogenesis. |
format | Online Article Text |
id | pubmed-8961633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89616332022-03-30 Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control Zhang, Yu Xia, Jiamin Liu, Min Chen, Bingyu Yang, Min Yu, Xiaoping Ou, Yu Li, Shurong Liu, Xindong Feng, Yi Su, Bingyin Huang, Sizhou Biomolecules Article Minichromosome maintenance protein 5 (MCM5) is a critical cell cycle regulator; its role in DNA replication is well known, but whether it is involved in the regulation of organogenesis in a cell cycle-independent way, is far from clear. In this study, we found that a loss of mcm5 function resulted in a mildly smaller liver, but that mcm5 overexpression led to liver bifida. Further, the data showed that mcm5 overexpression delayed endodermal migration in the ventral–dorsal axis and induced the liver bifida. Cell cycle analysis showed that a loss of mcm5 function, but not overexpression, resulted in cell cycle delay and increased cell apoptosis during gastrulation, implying that liver bifida was not the result of a cell cycle defect. In terms of its mechanism, our data proves that mcm5 represses the expression of cxcr4a, which sequentially causes a decrease in the expression of itgb1b during gastrulation. The downregulation of the cxcr4a-itgb1b cascade leads to an endodermal migration delay during gastrulation, as well as to the subsequent liver bifida during liver morphogenesis. In conclusion, our results suggest that in a cell cycle-independent way, mcm5 works as a gene expression regulator, either partially and directly, or indirectly repressing the expression of cxcr4a and the downstream gene itgb1b, to coordinate endodermal migration during gastrulation and liver location during liver organogenesis. MDPI 2022-02-10 /pmc/articles/PMC8961633/ /pubmed/35204787 http://dx.doi.org/10.3390/biom12020286 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Yu Xia, Jiamin Liu, Min Chen, Bingyu Yang, Min Yu, Xiaoping Ou, Yu Li, Shurong Liu, Xindong Feng, Yi Su, Bingyin Huang, Sizhou Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control |
title | Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control |
title_full | Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control |
title_fullStr | Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control |
title_full_unstemmed | Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control |
title_short | Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control |
title_sort | mcm5 represses endodermal migration through cxcr4a-itgb1b cascade instead of cell cycle control |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961633/ https://www.ncbi.nlm.nih.gov/pubmed/35204787 http://dx.doi.org/10.3390/biom12020286 |
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