PUBLICATION
Loss of the Nodal modulator Nomo results in chondrodysplasia in zebrafish
- Authors
- Cao, L., Li, L., Li, Y., Zhuang, J., Chen, Y., Luo, S., Wang, Y., Shi, Y., Chen, J., Gao, J., Zhu, X., Wan, Y., Li, F., Yuan, W., Mo, X., Ye, X., Wang, X., Zhou, Z., Dai, G., Jiang, Z., Zhu, P., Wu, X., Fan, X.
- ID
- ZDB-PUB-181213-5
- Date
- 2018
- Source
- Current Molecular Medicine 18(7): 448-458 (Journal)
- Registered Authors
- Keywords
- CRISPR/Cas9, chondrogenesis, nomo, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified*/genetics
- Animals, Genetically Modified*/metabolism
- Cartilage*/metabolism
- Cartilage*/pathology
- Chondrogenesis/genetics*
- Clustered Regularly Interspaced Short Palindromic Repeats
- Humans
- Membrane Proteins/deficiency*
- Osteochondrodysplasias*/genetics
- Osteochondrodysplasias*/metabolism
- Osteochondrodysplasias*/pathology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/deficiency*
- PubMed
- 30539698 Full text @ Curr. Mol. Med.
Citation
Cao, L., Li, L., Li, Y., Zhuang, J., Chen, Y., Luo, S., Wang, Y., Shi, Y., Chen, J., Gao, J., Zhu, X., Wan, Y., Li, F., Yuan, W., Mo, X., Ye, X., Wang, X., Zhou, Z., Dai, G., Jiang, Z., Zhu, P., Wu, X., Fan, X. (2018) Loss of the Nodal modulator Nomo results in chondrodysplasia in zebrafish. Current Molecular Medicine. 18(7):448-458.
Abstract
Background Transforming growth factor-β (TGF-β)/nodal signaling is involved in early embryonic patterning in vertebrates. Nodal modulator (Nomo, also called pM5) is a negative regulator of nodal signaling. Currently, the role of nomo gene in cartilage development in vertebrates remains unknown.
Methods Nomo mutants were generated in a knockout model of zebrafish by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) targeting of the fibronectin type III domain. The expression of related genes, which are critical for chondrogenesis, was analyzed by whole-mount in situ hybridization and qRT-PCR. Whole-mount alcian staining was performed to analyze the cartilage structure.
Results nomo is highly expressed in various tissues including the cartilage. We successfully constructed a zebrafish nomo knockout model. nomo homozygous mutants exhibited varying degrees of hypoplasia and dysmorphism on 4 and 5 dpf, which is similar to chondrodysplasia in humans. The key genes of cartilage and skeletal development, including sox9a, sox9b, dlx1a, dlx2a, osx, col10a1, and col11a2 were all downregulated in nomo mutants compared with the wildtype.
Conclusion The nomo gene positively regulates the expression of the master regulator and other key development genes involved in bone formation and cartilage development and it is essential for cartilage development in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping