Tubgcp3 Is Required for Retinal Progenitor Cell Proliferation During Zebrafish Development

Tubgcp3 Is Required for Retinal Progenitor Cell Proliferation During Zebrafish Development
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斑马鱼发育过程中视网膜祖细胞增殖需要 Tubgcp3

DOI:
10.3389/fnmol.2019.00126
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发表时间:
2019-05-24
影响因子:
4.8
通讯作者:
Zhong, Tao P.
Zhong, Tao P.
中科院分区:
医学2区
文献类型:
--
作者:
Li, Guobao;Jin, Daqing;Zhong, Tao P.

文献摘要

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中心体蛋白γ-微管蛋白复合物蛋白3(Tubgcp 3/GCP 3)是组装γ-微管蛋白小复合物(γ-TuSC)和γ-微管蛋白环复合物(γ-TuRC)所必需的,其在有丝分裂期间的有丝分裂纺锤体形成中起关键作用。然而,其在脊椎动物胚胎发育中的功能尚不清楚。在这里,我们使用CRISPR/Cas9系统产生了斑马鱼tubgcp 3突变体,并发现tubgcp 3突变体表现出小眼表型。Tubgcp 3是视网膜祖细胞(RPC)细胞周期进程所必需的,其缺失导致细胞周期停滞在有丝分裂(M)期。M期阻滞的RPC表现为异常的单极纺锤体和异常分布的中心粒和γ-微管蛋白。此外,这些RPC最终发生凋亡。我们的研究为Tubgcp 3的功能研究提供了体内模型,并阐明了中心体γ-微管蛋白复合物在脊椎动物发育中的作用。
The centrosomal protein gamma-tubulin complex protein 3 (Tubgcp3/GCP3) is required for the assembly of gamma-tubulin small complexes (gamma-TuSCs) and gamma-tubulin ring complexes (gamma-TuRCs), which play critical roles in mitotic spindle formation during mitosis. However, its function in vertebrate embryonic development is unknown. Here, we generated the zebrafish tubgcp3 mutants using the CRISPR/Cas9 system and found that the tubgcp3 mutants exhibited the small eye phenotype. Tubgcp3 is required for the cell cycle progression of retinal progenitor cells (RPCs), and its depletion caused cell cycle arrest in the mitotic (M) phase. The M-phase arrested RPCs exhibited aberrant monopolar spindles and abnormal distributed centrioles and gamma-tubulin. Moreover, these RPCs underwent apoptosis finally. Our study provides the in vivo model for the functional study of Tubgcp3 and sheds light on the roles of centrosomal gamma-tubulin complexes in vertebrate development.