Zebrafish cyclin Dx is required for development of motor neuron progenitors and its expression is regulated by hypoxia-inducible factor 2α

Cyclins play a central role in cell-cycle regulation; in mammals, the D family of cyclins consists of cyclin D1, D2 and D3. In Xenopus , only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progen...

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Veröffentlicht in:Scientific reports 2016-06, Vol.6 (1), p.28297-28297, Article 28297
Hauptverfasser: Lien, Huang-Wei, Yuan, Rey-Yue, Chou, Chih-Ming, Chen, Yi-Chung, Hung, Chin-Chun, Hu, Chin-Hwa, Hwang, Sheng-Ping L., Hwang, Pung-Pung, Shen, Chia-Ning, Chen, Chih-Lung, Cheng, Chia-Hsiung, Huang, Chang-Jen
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container_title Scientific reports
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creator Lien, Huang-Wei
Yuan, Rey-Yue
Chou, Chih-Ming
Chen, Yi-Chung
Hung, Chin-Chun
Hu, Chin-Hwa
Hwang, Sheng-Ping L.
Hwang, Pung-Pung
Shen, Chia-Ning
Chen, Chih-Lung
Cheng, Chia-Hsiung
Huang, Chang-Jen
description Cyclins play a central role in cell-cycle regulation; in mammals, the D family of cyclins consists of cyclin D1, D2 and D3. In Xenopus , only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progenitors during embryogenesis. It remains unknown whether zebrafish possess cyclin D3 or cyclin Dx. In this study, we identified a zebrafish ccndx gene encoding a protein which can form a complex with Cdk4. Through whole-mount in situ hybridization, we observed that zccndx mRNA is expressed in the motor neurons of hindbrain and spinal cord during development. Analysis of a 4-kb promoter sequence of the zccndx gene revealed the presence of HRE sites, which can be regulated by HIF2α. Morpholino knockdown of zebrafish Hif2α and cyclin Dx resulted in the abolishment of isl1 and oligo2 expression in the precursors of motor neurons and also disrupted axon growth. Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons.
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In Xenopus , only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progenitors during embryogenesis. It remains unknown whether zebrafish possess cyclin D3 or cyclin Dx. In this study, we identified a zebrafish ccndx gene encoding a protein which can form a complex with Cdk4. Through whole-mount in situ hybridization, we observed that zccndx mRNA is expressed in the motor neurons of hindbrain and spinal cord during development. Analysis of a 4-kb promoter sequence of the zccndx gene revealed the presence of HRE sites, which can be regulated by HIF2α. Morpholino knockdown of zebrafish Hif2α and cyclin Dx resulted in the abolishment of isl1 and oligo2 expression in the precursors of motor neurons and also disrupted axon growth. Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27323909</pmid><doi>10.1038/srep28297</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/136/368/2430
631/337/572/2102
Animals
Basic Helix-Loop-Helix Transcription Factors - physiology
Cell Proliferation
Cercopithecus aethiops
COS Cells
Cyclins - physiology
Gene Expression
Gene Expression Regulation, Developmental
HEK293 Cells
Humanities and Social Sciences
Humans
Mice
Motor Neurons - physiology
multidisciplinary
Neural Stem Cells - physiology
Neurogenesis
Science
Zebrafish - embryology
title Zebrafish cyclin Dx is required for development of motor neuron progenitors and its expression is regulated by hypoxia-inducible factor 2α
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