Rosales-Nieves Alicia E, Marín-Menguiano Miriam, López-Onieva Lourdes, Garrido-Maraver Juan, González-Reyes Acaimo
Centro Andaluz de Biología del Desarrollo, CSIC/Universidad Pablo de Olavide/JA, Sevilla, Spain.
PLoS Genet. 2025 Aug 25;21(8):e1011809. doi: 10.1371/journal.pgen.1011809. eCollection 2025 Aug.
Proper gonad development is a pre-requisite for gametogenesis and reproduction. During female gonad formation in Drosophila, the EGF receptor (EGFR) signalling pathway ensures the correct number of primordial germ cells (PGCs) populate the larval gonad. We study the gene pointed (pnt), which acts downstream of the EGFR receptor and belongs to the ETS transcription factor family, with a previously unknown function in gonadogenesis. We report that pnt is expressed in female larval gonads and later in the adult ovarian germline niche and that it is required to sustain proper gametogenesis. Loss of pnt function in female larval gonads, similar to the EGFR, induced PGC overproliferation. Conversely, we isolated a novel mutant allele gene, termed pntaga, which resulted in agametic gonads and ovaries. While pntaga embryos developed gonads containing a normal complement of PGCs, these are subsequently lost by apoptosis during late larval and pupal stages. Molecular characterization of pntaga revealed reduced expression levels of the different pnt isoforms, unveiling a complex autoregulatory network involving the three Pnt proteins. We propose that germline survival in Drosophila gonads requires a precise tuning of EGFR signalling to ensure the appropriate transcriptional activation of its target pnt.
正常的性腺发育是配子发生和繁殖的先决条件。在果蝇雌性性腺形成过程中,表皮生长因子受体(EGFR)信号通路确保有正确数量的原始生殖细胞(PGC)定殖于幼虫性腺。我们研究了基因“指向”(pnt),它在EGFR受体下游起作用,属于ETS转录因子家族,在性腺发生中具有此前未知的功能。我们报告称,pnt在雌性幼虫性腺中表达,随后在成年卵巢生殖系微环境中表达,并且它是维持正常配子发生所必需的。雌性幼虫性腺中pnt功能的丧失,与EGFR功能丧失类似,会诱导PGC过度增殖。相反,我们分离出一个新的突变等位基因,称为pntaga,它导致无配子性腺和卵巢。虽然pntaga胚胎发育出含有正常数量PGC的性腺,但这些PGC随后在幼虫后期和蛹期因凋亡而丢失。对pntaga的分子特征分析显示不同pnt异构体的表达水平降低,揭示了一个涉及三种Pnt蛋白的复杂自调节网络。我们提出,果蝇性腺中的生殖系存活需要对EGFR信号进行精确调节,以确保其靶标pnt的适当转录激活。