Linghui Cao: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Lingyu Li: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Yongqing Li: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Jian Zhuang: Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
Yu Chen: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Yuequn Wang: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Yan Shi: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Jimei Chen: Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
Xiaolan Zhu: Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
Yongqi Wan: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Fang Li: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Wuzhou Yuan: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Xiaoyang Mo: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Xiangli Ye: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Zuoqiong Zhou: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Guo Dai: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Zhigang Jiang: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Ping Zhu: Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
Xiushan Wu: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Xiongwei Fan: The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
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 zebrafishnomo 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.
