Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06519, USA.
Department of Genetics, Yale School of Medicine, New Haven, CT 06519, USA.
Genetics. 2021 Aug 26;219(1). doi: 10.1093/genetics/iyab091.
In many animals, germline development is initiated by proteins and RNAs that are expressed maternally. PIWI proteins and their associated small noncoding PIWI-interacting RNAs (piRNAs), which guide PIWI to target RNAs by base-pairing, are among the maternal components deposited into the germline of the Drosophila early embryo. Piwi has been extensively studied in the adult ovary and testis, where it is required for transposon suppression, germline stem cell self-renewal, and fertility. Consequently, loss of Piwi in the adult ovary using piwi-null alleles or knockdown from early oogenesis results in complete sterility, limiting investigation into possible embryonic functions of maternal Piwi. In this study, we show that the maternal Piwi protein persists in the embryonic germline through gonad coalescence, suggesting that maternal Piwi can regulate germline development beyond early embryogenesis. Using a maternal knockdown strategy, we find that maternal Piwi is required for the fertility and normal gonad morphology of female, but not male, progeny. Following maternal piwi knockdown, transposons were mildly derepressed in the early embryo but were fully repressed in the ovaries of adult progeny. Furthermore, the maternal piRNA pool was diminished, reducing the capacity of the PIWI/piRNA complex to target zygotic genes during embryogenesis. Examination of embryonic germ cell proliferation and ovarian gene expression showed that the germline of female progeny was partially masculinized by maternal piwi knockdown. Our study reveals a novel role for maternal Piwi in the germline development of female progeny and suggests that the PIWI/piRNA pathway is involved in germline sex determination in Drosophila.
在许多动物中,生殖细胞的发育是由母体表达的蛋白质和 RNA 启动的。PIWI 蛋白及其相关的小非编码 PIWI 相互作用 RNA(piRNA),通过碱基配对引导 PIWI 靶向 RNA,是被沉积到果蝇早期胚胎生殖系中的母体成分之一。Piwi 在成年卵巢和睾丸中被广泛研究,在那里它被需要用于转座子抑制、生殖干细胞自我更新和生育能力。因此,使用 piwi 缺失等位基因或从早期卵发生中敲低 Piwi 在成年卵巢中的表达会导致完全不育,限制了对母体 Piwi 可能的胚胎功能的研究。在这项研究中,我们表明母体 Piwi 蛋白在性腺融合过程中在胚胎生殖系中持续存在,这表明母体 Piwi 可以调节生殖系发育超出早期胚胎发生。使用母体敲低策略,我们发现母体 Piwi 对于雌性但不是雄性后代的生育能力和正常性腺形态是必需的。在母体 piwi 敲低后,转座子在早期胚胎中被轻度去抑制,但在成年后代的卵巢中被完全抑制。此外,母体 piRNA 池减少,降低了 PIWI/piRNA 复合物在胚胎发生期间靶向合子基因的能力。对胚胎生殖细胞增殖和卵巢基因表达的检查表明,母体 piwi 敲低导致雌性后代的生殖系部分雄性化。我们的研究揭示了母体 Piwi 在雌性后代生殖系发育中的新作用,并表明 PIWI/piRNA 途径参与了果蝇生殖系性别决定。