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 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.
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Huang-Wei
HW
Lien
Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 115, Taiwan.
Rey-Yue
RY
Yuan
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 115, Taiwan.
Chih-Ming
CM
Chou
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Yi-Chung
YC
Chen
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Chin-Chun
CC
Hung
Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan.
Chin-Hwa
CH
Hu
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Sheng-Ping L
SP
Hwang
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Pung-Pung
PP
Hwang
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Chia-Ning
CN
Shen
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Chih-Lung
CL
Chen
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 115, Taiwan.
Chia-Hsiung
CH
Cheng
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Chang-Jen
CJ
Huang
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D019556:COS Cells; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D016213:Cyclins / Q000502:physiology*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D015027:Zebrafish / Q000196:embryology; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D016213:Cyclins; D000099162:Endothelial PAS Domain-Containing Protein 1