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摘要
背景: 转化生长因子-β(TGF-β)/结信号参与脊椎动物早期胚胎发育。节点调制器(Nomo,也叫pm5)是节点信号的负调节器。目前,nomo基因在脊椎动物软骨发育中的作用尚不清楚。 方法: 在斑马鱼的敲除模型中,通过以纤维连接蛋白III型结构域为靶点的规则间隔短回文重复序列(CRISPR)/ CRISPR相关蛋白9(CRISPR/ Cas9)产生了nomo突变体。通过全贴装原位杂交和qRT-PCR分析了软骨发生的关键相关基因的表达。用阿新染色法对软骨结构进行了分析。 结果: Nomo在包括软骨在内的各种组织中高度表达。我们成功地构建了一个斑马鱼Nomo淘汰模型。Nomo纯合突变体在4和5 dpf上表现出不同程度的发育不全和畸形,这与人类软骨发育异常相似。与野生型相比,nomo突变体的软骨和骨骼发育的关键基因,包括sox9a、sox9b、dlx1a、dlx2a、osx、col10a1和col11a2均下调。 结论: nomo基因对参与骨形成和软骨发育的主调节器和其他关键发育基因的表达具有积极调节作用,对斑马鱼软骨发育至关重要。
关键词: Nomo,Crispr/Cas9,软骨发生,斑马鱼,冠细胞,原位。
Current Molecular Medicine
Title:Loss of the Nodal modulator Nomo results in chondrodysplasia in zebrafish
Volume: 18 Issue: 7
关键词: Nomo,Crispr/Cas9,软骨发生,斑马鱼,冠细胞,原位。
摘要: 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.
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Cite this article as:
Loss of the Nodal modulator Nomo results in chondrodysplasia in zebrafish, Current Molecular Medicine 2018; 18 (7) . https://dx.doi.org/10.2174/1566524019666181212095307
DOI https://dx.doi.org/10.2174/1566524019666181212095307 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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