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Functions of SMC2 in the Development of Zebrafish Liver

SMC2 (structural maintenance of chromosomes 2) is the core subunit of condensins, which play a central role in chromosome organization and segregation. However, the functions of SMC2 in embryonic development remain poorly understood, due to the embryonic lethality of homozygous SMC2(−/−) mice. Herei...

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Autores principales: Li, Xixi, Song, Guili, Zhao, Yasong, Ren, Jing, Li, Qing, Cui, Zongbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465584/
https://www.ncbi.nlm.nih.gov/pubmed/34572426
http://dx.doi.org/10.3390/biomedicines9091240
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author Li, Xixi
Song, Guili
Zhao, Yasong
Ren, Jing
Li, Qing
Cui, Zongbin
author_facet Li, Xixi
Song, Guili
Zhao, Yasong
Ren, Jing
Li, Qing
Cui, Zongbin
author_sort Li, Xixi
collection PubMed
description SMC2 (structural maintenance of chromosomes 2) is the core subunit of condensins, which play a central role in chromosome organization and segregation. However, the functions of SMC2 in embryonic development remain poorly understood, due to the embryonic lethality of homozygous SMC2(−/−) mice. Herein, we explored the roles of SMC2 in the liver development of zebrafish. The depletion of SMC2, with the CRISPR/Cas9-dependent gene knockout approach, led to a small liver phenotype. The specification of hepatoblasts was unaffected. Mechanistically, extensive apoptosis occurred in the liver of SMC2 mutants, which was mainly associated with the activation of the p53-dependent apoptotic pathway. Moreover, an aberrant activation of a series of apoptotic pathways in SMC2 mutants was involved in the defective chromosome segregation and subsequent DNA damage. Therefore, our findings demonstrate that SMC2 is necessary for zebrafish liver development.
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spelling pubmed-84655842021-09-27 Functions of SMC2 in the Development of Zebrafish Liver Li, Xixi Song, Guili Zhao, Yasong Ren, Jing Li, Qing Cui, Zongbin Biomedicines Article SMC2 (structural maintenance of chromosomes 2) is the core subunit of condensins, which play a central role in chromosome organization and segregation. However, the functions of SMC2 in embryonic development remain poorly understood, due to the embryonic lethality of homozygous SMC2(−/−) mice. Herein, we explored the roles of SMC2 in the liver development of zebrafish. The depletion of SMC2, with the CRISPR/Cas9-dependent gene knockout approach, led to a small liver phenotype. The specification of hepatoblasts was unaffected. Mechanistically, extensive apoptosis occurred in the liver of SMC2 mutants, which was mainly associated with the activation of the p53-dependent apoptotic pathway. Moreover, an aberrant activation of a series of apoptotic pathways in SMC2 mutants was involved in the defective chromosome segregation and subsequent DNA damage. Therefore, our findings demonstrate that SMC2 is necessary for zebrafish liver development. MDPI 2021-09-16 /pmc/articles/PMC8465584/ /pubmed/34572426 http://dx.doi.org/10.3390/biomedicines9091240 Text en © 2021 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
Li, Xixi
Song, Guili
Zhao, Yasong
Ren, Jing
Li, Qing
Cui, Zongbin
Functions of SMC2 in the Development of Zebrafish Liver
title Functions of SMC2 in the Development of Zebrafish Liver
title_full Functions of SMC2 in the Development of Zebrafish Liver
title_fullStr Functions of SMC2 in the Development of Zebrafish Liver
title_full_unstemmed Functions of SMC2 in the Development of Zebrafish Liver
title_short Functions of SMC2 in the Development of Zebrafish Liver
title_sort functions of smc2 in the development of zebrafish liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465584/
https://www.ncbi.nlm.nih.gov/pubmed/34572426
http://dx.doi.org/10.3390/biomedicines9091240
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