Centrosomal protein FOR20 is essential for cilia-dependent development in zebrafish embryos
Centrosomal protein FOR20 is essential for cilia-dependent development in zebrafish embryos
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中心体蛋白 FOR20 对于斑马鱼胚胎纤毛依赖性发育至关重要。
DOI：
10.1096/fj.201801235rr
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发表时间：
2019-03-01
期刊：
影响因子：
4.8
通讯作者：
Zhou, Tianhua
中科院分区：
文献类型：
--
作者：
Xie, Shanshan;Jin, Juan;Zhou, Tianhua
中心体蛋白在纤毛发生中起着重要作用。许多中心体蛋白的突变已被证明是导致发育缺陷和纤毛相关疾病的原因。中心体蛋白成纤维细胞生长因子受体1癌基因伴侣相关蛋白20 kDa（FOR 20）是哺乳动物细胞和单细胞真核生物草履虫纤毛发生的关键，然而，在脊椎动物发育的生物学意义FOR 20仍不清楚。我们克隆了斑马鱼for 20基因的同源物，发现for 20 mRNA在斑马鱼发育早期的纤毛组织中富集。在斑马鱼中，通过吗啉寡核苷酸敲低for 20导致多种纤毛表型，包括弯曲体、脑积水、心包水肿、肾囊肿和左右不对称缺陷。20例吗啡样变形体的枯否囊泡和前肾管纤毛数量和长度减少。高速视频显微镜显示，大多数20种吗啡肽的纤毛都是持续麻痹或搏动的。为了证实for 20 morphants的纤毛表型，我们使用CRISPR/Cas9系统破坏斑马鱼for 20基因。for 20突变体表现出多种纤毛表型，类似于for 20 morphant中的缺陷。for 20突变体和突变体的所有这些表型都被for 20 mRNA的外源表达显著逆转。综上所述，这些数据表明，在斑马鱼胚胎发生过程中，FOR 20是纤毛介导的过程所必需的。Jin，J.，徐志，黄，Y.，张伟，赵，L.，洛湖J.，彭，J，刘伟，王福，Shu，Q.，Zhou，T.中心体蛋白FOR 20是斑马鱼胚胎纤毛依赖性发育所必需的。
Centrosomal proteins play critical roles in ciliogenesis. Mutations in many centrosomal proteins have been documented to contribute to developmental defects and cilium-related diseases. Centrosomal protein fibroblast growth factor receptor 1 oncogene partner-related protein of 20 kDa (FOR20) is crucial for ciliogenesis in mammalian cells and the unicellular eukaryote Paramecium; however, the biologic significance of FOR20 in vertebrate development remains unclear. We cloned the zebrafish homolog of the for20 gene and found that for20 mRNA is enriched in ciliated tissues during early zebrafish development. Knockdown of for20 by morpholino oligonucleotides in zebrafish results in multiple ciliary phenotypes, including curved body, hydrocephaly, pericardial edema, kidney cysts, and left-right asymmetry defects. for20 morphants show reduced number and length of cilia in Kupffer's vesicle and pronephric ducts. High-speed video microscopy reveals that cilia in most for20 morphants are consistently paralyzed or beat arrhythmically. To confirm the ciliary phenotypes of for20 morphants, we used the CRISPR/Cas9 system to disrupt for20 gene in zebrafish. for20 mutants exhibit multiple ciliary phenotypes resembling the defects in for20 morphants. All of these phenotypes in for20 morphants and mutants are significantly reversed by exogenous expression of for20 mRNA. Taken together, these data suggest that FOR20 is required for cilium-mediated processes during zebrafish embryogenesis.Xie, S., Jin, J., Xu, Z., Huang, Y., Zhang, W., Zhao, L., Lo, L. J., Peng, J., Liu, W., Wang, F., Shu, Q., Zhou, T. Centrosomal protein FOR20 is essential for cilia-dependent development in zebrafish embryos.