Division of Life Science, Graduate School of Science and Engineering, Saitama University, Shimo-Okubo 255, Sakura-ku, Saitama, 338-8570, Japan.
Cell Architecture Laboratory, National Institute of Genetics, Yata 1111, Mishima, Shizuoka, 411-8540, Japan.
Sci Rep. 2024 Oct 9;14(1):23602. doi: 10.1038/s41598-024-74134-9.
The paralogs 9-13 Hox genes in mouse HoxA and HoxD clusters are critical for limb development. When both HoxA and HoxD clusters are deleted in mice, significant limb truncation is observed compared to the phenotypes of single and compound mutants of Hox9-13 genes in these clusters. In zebrafish, mutations in hox13 genes in HoxA- and HoxD-related clusters result in abnormal morphology of pectoral fins, homologous to forelimbs. However, the effect of the simultaneous deletions of entire HoxA- and HoxD-related clusters on pectoral fin development remains unknown. Here, we generated mutants with several combinations of hoxaa, hoxab, and hoxda cluster deletions and analyzed the pectoral fin development. In hoxaa;hoxab;hoxda larvae, the endoskeletal disc and the fin-fold are significantly shortened in developing pectoral fins. In addition, we show that this anomaly is due to defects in the pectoral fin growth after the fin bud formation. Furthermore, in the surviving adult mutants, micro-CT scanning reveals defects in the posterior portion of the pectoral fin which is thought to represent latent regions of the limb. Our results further support that the functional role of HoxA and HoxD clusters is conserved in the paired appendage formation in bony fishes.
小鼠 HoxA 和 HoxD 簇中的 paralogs 9-13 Hox 基因对于肢体发育至关重要。当小鼠中同时删除 HoxA 和 HoxD 簇时，与这些簇中 Hox9-13 基因的单突变和复合突变表型相比，观察到明显的肢体截断。在斑马鱼中，HoxA-和 HoxD 相关簇中的 hox13 基因突变导致胸鳍形态异常，类似于前肢。然而，同时删除整个 HoxA-和 HoxD 相关簇对胸鳍发育的影响仍不清楚。在这里，我们生成了具有 hoxaa、hoxab 和 hoxda 簇缺失的几种组合的突变体，并分析了胸鳍发育。在 hoxaa；hoxab；hoxda 幼虫中，发育中的胸鳍的内骨骼盘和鳍褶明显缩短。此外，我们表明这种异常是由于鳍芽形成后胸鳍生长的缺陷引起的。此外，在幸存的成年突变体中，微 CT 扫描显示胸鳍后部存在缺陷，这被认为代表肢体的潜在区域。我们的结果进一步支持了 HoxA 和 HoxD 簇在硬骨鱼的成对附肢形成中的功能作用是保守的。
