Cell Architecture Laboratory, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Division of Life Science, Graduate School of Science and Engineering, Saitama University, Shimo-Okubo 255, Sakura-ku, Saitama 338-8570, Japan.
Development. 2024 Jul 15;151(14). doi: 10.1242/dev.202854. Epub 2024 Jul 12.
The vertebral column is a characteristic structure of vertebrates. Genetic studies in mice have shown that Hox-mediated patterning plays a key role in specifying discrete anatomical regions of the vertebral column. Expression pattern analyses in several vertebrate embryos have provided correlative evidence that the anterior boundaries of Hox expression coincide with distinct anatomical vertebrae. However, because functional analyses have been limited to mice, it remains unclear which Hox genes actually function in vertebral patterning in other vertebrates. In this study, various zebrafish Hox mutants were generated for loss-of-function phenotypic analysis to functionally decipher the Hox code responsible for the zebrafish anterior vertebrae between the occipital and thoracic vertebrae. We found that Hox genes in HoxB- and HoxC-related clusters participate in regulating the morphology of the zebrafish anterior vertebrae. In addition, medaka hoxc6a was found to be responsible for anterior vertebral identity, as in zebrafish. Based on phenotypic similarities with Hoxc6 knockout mice, our results suggest that the Hox patterning system, including at least Hoxc6, may have been functionally established in the vertebral patterning of the common ancestor of ray-finned and lobe-finned fishes.
脊柱是脊椎动物的特征结构。在小鼠中的遗传研究表明,Hox 介导的模式形成在指定脊椎的离散解剖区域中起着关键作用。在几种脊椎动物胚胎中的表达模式分析提供了相关证据,表明 Hox 表达的前边界与独特的解剖学椎体一致。然而,由于功能分析仅限于小鼠,因此尚不清楚哪些 Hox 基因实际上在其他脊椎动物的脊椎模式形成中起作用。在这项研究中,生成了各种斑马鱼 Hox 突变体进行功能丧失表型分析,以功能上解析负责斑马鱼头骨和胸椎之间的前脊椎的 Hox 代码。我们发现,HoxB 和 HoxC 相关簇中的 Hox 基因参与调节斑马鱼前脊椎的形态。此外,还发现 medaka hoxc6a 负责前脊椎的身份,与斑马鱼一样。基于与 Hoxc6 敲除小鼠的表型相似性,我们的结果表明,包括至少 Hoxc6 在内的 Hox 模式形成系统可能已经在射线鳍鱼和肺鱼的共同祖先的脊椎模式形成中得到了功能上的建立。