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.
Abstract
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.
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.
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.
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
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes