Department of Physiology & Neurobiology, University of Connecticut, Storrs, CT 06269, USA.
Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
Development. 2024 Mar 1;151(5). doi: 10.1242/dev.202276. Epub 2024 Feb 28.
Drosophila matrix metalloproteinase 2 (MMP2) is specifically expressed in posterior follicle cells of stage-14 egg chambers (mature follicles) and is crucial for the breakdown of the follicular wall during ovulation, a process that is highly conserved from flies to mammals. The factors that regulate spatiotemporal expression of MMP2 in follicle cells remain unknown. Here, we demonstrate crucial roles for the ETS-family transcriptional activator Pointed (Pnt) and its endogenous repressor Yan in the regulation of MMP2 expression. We found that Pnt is expressed in posterior follicle cells and overlaps with MMP2 expression in mature follicles. Genetic analysis demonstrated that pnt is both required and sufficient for MMP2 expression in follicle cells. In addition, Yan was temporally upregulated in stage-13 follicle cells to fine-tune Pnt activity and MMP2 expression. Furthermore, we identified a 1.1 kb core enhancer that is responsible for the spatiotemporal expression of MMP2 and contains multiple pnt/yan binding motifs. Mutation of pnt/yan binding sites significantly impaired the Mmp2 enhancer activity. Our data reveal a mechanism of transcriptional regulation of Mmp2 expression in Drosophila ovulation, which could be conserved in other biological systems.
果蝇基质金属蛋白酶 2（MMP2）特异性表达于 14 期卵囊中（成熟滤泡）的后滤泡细胞，对于卵母细胞排出过程中滤泡壁的分解至关重要，这一过程在从果蝇到哺乳动物中都高度保守。然而，调节滤泡细胞中 MMP2 时空表达的因素仍不清楚。在这里，我们证明了 ETS 家族转录激活因子 Pointed（Pnt）及其内源性抑制因子 Yan 在调节 MMP2 表达中的关键作用。我们发现 Pnt 在成熟滤泡的后滤泡细胞中表达，并与 MMP2 表达重叠。遗传分析表明，pnt 对于滤泡细胞中 MMP2 的表达既需要又充分。此外，Yan 在 13 期滤泡细胞中被暂时上调，以微调 Pnt 活性和 MMP2 表达。此外，我们鉴定了一个 1.1kb 的核心增强子，负责 MMP2 的时空表达，并包含多个 pnt/yan 结合基序。pnt/yan 结合位点的突变显著削弱了 Mmp2 增强子的活性。我们的数据揭示了果蝇排卵中 MMP2 表达的转录调控机制，这可能在其他生物系统中保守。
