Mu Zhiyu, Zheng Pengfei, Liu Shuangyu, Kang Yunsi, Xie Haibo
Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, 266003, China.
Key Laboratory of Evolution and Marine Biodiversity of the Ministry of Education, Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, 266003, China.
Dev Biol. 2025 Jan;517:148-156. doi: 10.1016/j.ydbio.2024.09.006. Epub 2024 Sep 18.
PLK4 plays a crucial role in centriole duplication, which is essential for maintaining cellular processes such as cell division, cytoskeletal stability, and cilia formation. However, the mechanisms of PLK4 remain incompletely understood, especially in the embryonic development of vertebrate species. In this study, we observed that Plk4 dysfunction led to abnormal embryonic development in zebrafish, characterized by symptoms such as dark and wrinkled skin, microphthalmia, and body axis curvature. In plk4 mutants, defects in centriole duplication led to abnormal cell division, apoptosis, and ciliogenesis defects. Moreover, overexpression of plk4 in zebrafish embryos caused excessive centrosome amplification, disrupting embryonic gastrulation through abnormal cell division and ultimately resulting in embryonic lethality. Furthermore, we identified the "cryptic" polo box (CPB) domain, consisting of two PBs (PB1 and PB2), as the critical centrosome localization domain of Plk4. Surprisingly, overexpression of these two PB domains alone was sufficient to induce embryonic lethality. Additionally, we discovered a truncated form of CPB that localizes to the centrosome without causing defects in embryonic development. Our results demonstrate that Plk4 tightly controls centriole duplication, which is essential for early embryonic development in zebrafish.
PLK4在中心粒复制中发挥关键作用，而中心粒复制对于维持细胞分裂、细胞骨架稳定性和纤毛形成等细胞过程至关重要。然而，PLK4的机制仍未完全了解，尤其是在脊椎动物物种的胚胎发育过程中。在本研究中，我们观察到Plk4功能障碍导致斑马鱼胚胎发育异常，其特征为皮肤暗黑起皱、小眼症和体轴弯曲等症状。在plk4突变体中，中心粒复制缺陷导致细胞分裂异常、细胞凋亡和纤毛发生缺陷。此外，斑马鱼胚胎中plk4的过表达导致中心体过度扩增，通过异常细胞分裂破坏胚胎原肠胚形成，最终导致胚胎致死。此外，我们鉴定出由两个PB（PB1和PB2）组成的“隐秘”polo框（CPB）结构域，作为Plk4的关键中心体定位结构域。令人惊讶的是，单独过表达这两个PB结构域就足以诱导胚胎致死。此外，我们发现了一种截短形式的CPB，其定位于中心体但不会导致胚胎发育缺陷。我们的结果表明，Plk4严格控制中心粒复制，这对于斑马鱼的早期胚胎发育至关重要。
