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Loss of the Nodal modulator Nomo results in chondrodysplasia in zebrafish.
Cao, Linghui; Li, Lingyu; Li, Yongqing; Zhuang, Jian; Chen, Yu; Wang, Yuequn; Shi, Yan; Chen, Jimei; Zhu, Xiaolan; Wan, Yongqi; Li, Fang; Yuan, Wuzhou; Mo, Xiaoyang; Ye, Xiangli; Zhou, Zuoqiong; Dai, Guo; Jiang, Zhigang; Zhu, Ping; Wu, Xiushan; Fan, Xiongwei.
Afiliación
  • Cao L; 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, Changs
  • Li L; 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, Changs
  • Li Y; 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, Changs
  • Zhuang J; Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
  • Chen Y; 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, Changs
  • Wang Y; 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, Changs
  • Shi Y; 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, Changs
  • Chen J; Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
  • Zhu X; Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
  • Wan Y; 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, Changs
  • Li F; 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, Changs
  • Yuan W; 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, Changs
  • Mo X; 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, Changs
  • Ye X; 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, Changs
  • Zhou Z; 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, Changs
  • Dai G; Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
  • Jiang Z; 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, Changs
  • Zhu P; 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, Changs
  • Wu X; Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
  • Fan X; 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, Changs
Curr Mol Med ; 18(7): 448-458, 2018.
Article en En | MEDLINE | ID: mdl-30539698
ABSTRACT

BACKGROUND:

Transforming growth factor-ß (TGF-ß)/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.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Osteocondrodisplasias / Pez Cebra / Animales Modificados Genéticamente / Cartílago / Condrogénesis / Proteínas de Pez Cebra / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Curr Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Asunto principal: Osteocondrodisplasias / Pez Cebra / Animales Modificados Genéticamente / Cartílago / Condrogénesis / Proteínas de Pez Cebra / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Curr Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article