Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish
We have previously observed the predominant expression of nucleoporin 62-like (Nup62l<i>)</i> mRNA in the pharyngeal region of zebrafish, which raises the question whether Nup62l has important implications in governing the morphogenesis of pharyngeal arches (PA) in zebrafish. Herein, we...
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doaj-c125d1ddcbe1472a80e481b9e9cdf5a82020-11-24T20:52:50ZengMDPI AGCells2073-44092019-09-0189103810.3390/cells8091038cells8091038Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in ZebrafishXiaojie Yang0Xixi Li1Qilin Gu2Qing Li3Zongbin Cui4State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaWe have previously observed the predominant expression of nucleoporin 62-like (Nup62l<i>)</i> mRNA in the pharyngeal region of zebrafish, which raises the question whether Nup62l has important implications in governing the morphogenesis of pharyngeal arches (PA) in zebrafish. Herein, we explored the functions of Nup62l in PA development. The disruption of Nup62l with a CRISPR/Cas9-dependent gene knockout approach led to defective PA, which was characterized by a thinned and shortened pharyngeal region and a significant loss of pharyngeal cartilages. During pharyngeal cartilage formation, prechondrogenic condensation and chondrogenic differentiation were disrupted in homozygous<i> nup62l</i>-mutants, while the specification and migration of cranial neural crest cells (CNCCs) were unaffected. Mechanistically, the impaired PA region of <i>nup62l</i>-mutants underwent extensive apoptosis, which was mainly dependent on activation of p53-dependent apoptotic pathway. Moreover, aberrant activation of a series of apoptotic pathways in <i>nup62l</i>-mutants is closely associated with the inactivation of Wnt/β-catenin signaling. Thus, these findings suggest that the regulation of Wnt/β-catenin activity by Nup62l is crucial for PA formation in zebrafish.https://www.mdpi.com/2073-4409/8/9/1038Nup62lcraniofacial developmentpharyngeal archesWnt/β-catenin signalingapoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaojie Yang Xixi Li Qilin Gu Qing Li Zongbin Cui |
spellingShingle |
Xiaojie Yang Xixi Li Qilin Gu Qing Li Zongbin Cui Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish Cells Nup62l craniofacial development pharyngeal arches Wnt/β-catenin signaling apoptosis |
author_facet |
Xiaojie Yang Xixi Li Qilin Gu Qing Li Zongbin Cui |
author_sort |
Xiaojie Yang |
title |
Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish |
title_short |
Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish |
title_full |
Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish |
title_fullStr |
Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish |
title_full_unstemmed |
Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/β-Catenin Signaling and Apoptotic Homeostasis in Zebrafish |
title_sort |
nucleoporin 62-like protein is required for the development of pharyngeal arches through regulation of wnt/β-catenin signaling and apoptotic homeostasis in zebrafish |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2019-09-01 |
description |
We have previously observed the predominant expression of nucleoporin 62-like (Nup62l<i>)</i> mRNA in the pharyngeal region of zebrafish, which raises the question whether Nup62l has important implications in governing the morphogenesis of pharyngeal arches (PA) in zebrafish. Herein, we explored the functions of Nup62l in PA development. The disruption of Nup62l with a CRISPR/Cas9-dependent gene knockout approach led to defective PA, which was characterized by a thinned and shortened pharyngeal region and a significant loss of pharyngeal cartilages. During pharyngeal cartilage formation, prechondrogenic condensation and chondrogenic differentiation were disrupted in homozygous<i> nup62l</i>-mutants, while the specification and migration of cranial neural crest cells (CNCCs) were unaffected. Mechanistically, the impaired PA region of <i>nup62l</i>-mutants underwent extensive apoptosis, which was mainly dependent on activation of p53-dependent apoptotic pathway. Moreover, aberrant activation of a series of apoptotic pathways in <i>nup62l</i>-mutants is closely associated with the inactivation of Wnt/β-catenin signaling. Thus, these findings suggest that the regulation of Wnt/β-catenin activity by Nup62l is crucial for PA formation in zebrafish. |
topic |
Nup62l craniofacial development pharyngeal arches Wnt/β-catenin signaling apoptosis |
url |
https://www.mdpi.com/2073-4409/8/9/1038 |
work_keys_str_mv |
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