The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, Jiangsu 210096, China.
The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, Jiangsu 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226019, China.
J Genet Genomics. 2022 Jul;49(7):636-644. doi: 10.1016/j.jgg.2021.12.010. Epub 2022 Jan 10.
The highly conserved doublesex (dsx) and doublesex/mab-3 related (Dmrt) genes control sexually dimorphic traits across animals. The dsx gene encodes sex-specific transcription factors, Dsx in males and Dsx in females, which function differentially and often oppositely to establish sexual dimorphism. Here, we report that mutations in dsx, or overexpression of dsx, result in abnormal distribution of the basement membrane (BM) protein Collagen IV in the fat body. We find that Dsx isoforms regulate the expression of Collagen IV in the fat body and its secretion into the BM of other tissues. We identify the procollagen lysyl hydroxylase (dPlod) gene, which is involved in the biosynthesis of Collagen IV, as a direct target of Dsx. We further show that Dsx regulates Collagen IV through dPlod-dependent and independent pathways. These findings reveal how Dsx isoforms function in the secretory fat body to regulate Collagen IV and remotely establish sexual dimorphism.
高度保守的 doublesex (dsx) 和 doublesex/mab-3 相关 (Dmrt) 基因控制着动物的性别二态性特征。dsx 基因编码性别特异性转录因子，男性中的 Dsx 和女性中的 Dsx，它们以不同的方式和通常相反的方式发挥作用，以建立性别二态性。在这里，我们报告 dsx 突变或 dsx 的过表达导致脂肪体中基底膜 (BM) 蛋白 Collagen IV 的异常分布。我们发现 Dsx 同工型调节脂肪体中 Collagen IV 的表达及其分泌到其他组织的 BM 中。我们鉴定出参与 Collagen IV 生物合成的 procollagen 赖氨酸羟化酶 (dPlod) 基因是 Dsx 的直接靶标。我们进一步表明 Dsx 通过 dPlod 依赖和独立的途径调节 Collagen IV。这些发现揭示了 Dsx 同工型如何在分泌性脂肪体中发挥作用，以调节 Collagen IV 并远程建立性别二态性。
