Cyclin-dependent kinase 21 is a novel regulator of proliferation and meiosis in the male germline of zebrafish.
Cyclin-dependent kinase 21 is a novel regulator of proliferation and meiosis in the male germline of zebrafish.
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DOI：
10.1530/rep-18-0386
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发表时间：
2019-04
期刊：
影响因子：
3.8
通讯作者：
Kaitlyn A. Webster;Katrin Henke;Delaney M Ingalls;Adeeba Nahrin;M. Harris;K. Siegfried
中科院分区：
文献类型：
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作者：
Kaitlyn A. Webster;Katrin Henke;Delaney M Ingalls;Adeeba Nahrin;M. Harris;K. Siegfried
生殖细胞的分化和维持依赖于有丝分裂和减数分裂进程的复杂调控。细胞周期蛋白依赖性激酶（CDK）及其活化细胞周期蛋白伴侣在调节组织（包括生殖细胞）细胞周期进程中具有特殊作用。关于斑马鱼中CDK/细胞周期蛋白的功能或生殖细胞维持和分化的调控知之甚少。在斑马鱼性腺发育缺陷的正向遗传筛查中，发现了一个破坏cdk 21（细胞周期蛋白依赖性激酶21）的突变，该突变导致性腺发育不全、生育力降低和雌性性别鉴定失败。cdk 21基因是鱼类特有的，尽管编码的蛋白质与D-cyclin伴侣Cdk 4和Cdk 6相关，这是已知的G1细胞周期调节因子。在睾丸中，cdk 21突变体生殖细胞表现出细胞周期缺陷，如增殖减少，减数分裂延长和精子分化延迟。此外，cdk 21突变体在繁殖后不能维持生殖细胞。基于这些发现，我们认为cdk 21通过减数分裂和睾丸生殖干细胞的激活来调节精原细胞的增殖和进展。此外，我们研究了cdk 4和cdk 6在斑马鱼发育中的作用，发现它们在性腺中有不同的表达模式。突变体分析表明cdk 6是幼虫期以后生存所必需的。相反，cdk 4突变体是可行的，但都是男性，繁殖成功率低，精子过剩。我们的分析表明，斑马鱼携带cdk 4/6家族的三个基因，cdk 4，cdk 6和cdk 21，其中cdk 21在睾丸生殖细胞发育中具有重要作用。
Germ cell differentiation and maintenance relies on complex regulation of mitotic and meiotic progression. Cyclin-dependent kinases (CDKs) and their activating cyclin partners are known to have specialized roles in regulating cell cycle progression across tissues, including germ cells. Very little is known about CDK/cyclin function in zebrafish or the regulation of germ cell maintenance and differentiation. In a forward genetic screen for gonadogenesis defects in zebrafish, a mutation disrupting cdk21 (cyclin-dependent kinase 21) was identified, which caused gonad hypoplasia, reduced fertility and failure of female sex specification. The cdk21 gene is unique to fishes, though the encoded protein is related to the D-cyclin partners Cdk4 and Cdk6, which are known G1 cell cycle regulators. In the testis, cdk21 mutant germ cells exhibited cell cycle defects such as diminished proliferation, prolonged meiosis and delayed sperm differentiation. Furthermore, cdk21 mutants failed to maintain germ cells following breeding. Based on these findings, we propose that cdk21 regulates spermatogonial proliferation, progression through meiosis and germline stem cell activation in the testis. In addition, we investigated cdk4 and cdk6 in zebrafish development and found that each has distinct expression patterns in the gonads. Mutant analysis demonstrated that cdk6 was necessary for viability beyond larval stages. In contrast, cdk4 mutants were viable but were all male with low breeding success and sperm overabundance. Our analysis demonstrated that zebrafish harbor three genes of the cdk4/6 family, cdk4, cdk6 and cdk21, with cdk21 having an essential role in germ cell development in the testis.