Galletta Brian J, Konstantinidou Parthena, Haase Astrid D, Rusan Nasser M
Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
RNA Biology Section, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA.
G3 (Bethesda). 2025 Feb 5;15(2). doi: 10.1093/g3journal/jkae275.
The Sperm Neck provides a stable connection between the sperm head and tail, which is critical for fertility in species with flagellated sperm. Within the Sperm Neck, the Head-Tail Coupling Apparatus serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of the Drosophila melanogaster genome that contain genetic elements that influence Head-Tail Coupling Apparatus formation, we undertook a 2 part screen using the Drosophila Deficiency kit. For this screen, we utilized a sensitized genetic background that overexpresses the pericentriolar material regulatory protein Pericentrin-Like Protein. We had previously shown that Pericentrin-Like Protein overexpression disrupts the head-tail connection in some spermatids, but not to a degree sufficient to reduce fertility. In the first step of the screen, we tested for deficiencies that in combination with Pericentrin-Like Protein overexpression causes a reduction in fertility. We ultimately identified 11 regions of the genome that resulted in an enhanced fertility defect when combined with Pericentrin-Like Protein overexpression. In the second step of the screen, we tested these deficiencies for their ability to enhance the head-tail connection defect caused by Pericentrin-Like Protein overexpression, finding 6 genomic regions. We then tested smaller deficiencies to narrow the region of the genome that contained these enhancers and examined the expression patterns of the genes within these deficiencies using publicly available datasets of Drosophila tissue RNAseq and Drosophila testes snRNAseq. In total, our analysis suggests that some deficiencies may contain single genes that influence Head-Tail Coupling Apparatus formation or fertility, while other deficiencies appear to be genomic regions rich in testis-expressed genes that might affect the Head-Tail Coupling Apparatus through complex, multigene interactions.
精子颈部在精子头部和尾部之间提供了稳定的连接,这对于具有鞭毛精子的物种的生育能力至关重要。在精子颈部,头尾耦合装置通过中心粒作为细胞核(头部)和轴丝(尾部)之间的关键连接。为了鉴定黑腹果蝇基因组中包含影响头尾耦合装置形成的遗传元件的区域,我们使用果蝇缺失试剂盒进行了两部分筛选。对于此筛选,我们利用了一种敏感的遗传背景,该背景过表达中心粒周围物质调节蛋白类中心粒蛋白。我们之前已经表明,类中心粒蛋白的过表达会破坏一些精子细胞中的头尾连接,但程度不足以降低生育能力。在筛选的第一步中,我们测试了与类中心粒蛋白过表达相结合会导致生育能力下降的缺失。我们最终鉴定出基因组中的11个区域,当与类中心粒蛋白过表达相结合时,这些区域会导致生育缺陷增强。在筛选的第二步中,我们测试了这些缺失增强类中心粒蛋白过表达引起的头尾连接缺陷的能力,发现了6个基因组区域。然后,我们测试了更小的缺失以缩小包含这些增强子的基因组区域,并使用公开可用的果蝇组织RNA测序和果蝇睾丸单细胞核RNA测序数据集检查这些缺失内基因的表达模式。总的来说,我们的分析表明,一些缺失可能包含影响头尾耦合装置形成或生育能力的单个基因,而其他缺失似乎是富含睾丸表达基因的基因组区域,这些区域可能通过复杂的多基因相互作用影响头尾耦合装置。