The female-specific Doublesex isoform regulates pleiotropic transcription factors to pattern genital development in Drosophila
The female-specific Doublesex isoform regulates pleiotropic transcription factors to pattern genital development in Drosophila
复制标题
DOI：
10.1242/dev.055731
复制
发表时间：
2011-03-15
期刊：
影响因子：
4.6
通讯作者：
Siegal, Mark L.
中科院分区：
文献类型：
--
作者：
Chatterjee, Sujash S.;Uppendahl, Locke D.;Siegal, Mark L.
推动动物生殖器形态发生的调控网络必须整合性别身份和位置信息。尽管控制果蝇体细胞性别认同的遗传层次已经被很好地理解，但它控制组织特异性基因活动的机制被知道的案例很少。在果蝇中，性别决定层次终止于双性基因(Dsx)，该基因通过其转录本的选择性剪接产生性别特异的转录因子。为了确定驱动生殖器性别二型性发育的性别特异表达基因，我们在早期形态发生的三个时间点对每个性别解剖的生殖器成像盘进行了全基因组转录图谱。使用严格的统计阈值，我们识别出在所有三个时间点都有性别差异转录水平的23个基因，其中13个编码转录因子，这是一个显著的丰富。在此，我们重点研究了三种性别特异表达的转录因子，它们分别由LZ、Drop(DR)和AP-2编码。我们发现，在女性生殖器盘中，DSX激活LZ并抑制DR和AP-2。我们进一步证明，dsx对DR的调节介导了先前在男性生殖器盘中发现的成纤维细胞生长因子无分支的表达。我们在生殖盘中失去LZ或DR功能时观察到的表型解释了DSX突变果蝇中特定结构的存在或缺失，从而解释了之前令人困惑的观察结果。我们的表达数据的时间进程也为阐明性别特异性转录因子下游的调控网络奠定了基础。
Regulatory networks driving morphogenesis of animal genitalia must integrate sexual identity and positional information. Although the genetic hierarchy that controls somatic sexual identity in the fly Drosophila melanogaster is well understood, there are very few cases in which the mechanism by which it controls tissue-specific gene activity is known. In flies, the sex-determination hierarchy terminates in the doublesex (dsx) gene, which produces sex-specific transcription factors via alternative splicing of its transcripts. To identify sex-specifically expressed genes downstream of dsx that drive the sexually dimorphic development of the genitalia, we performed genome-wide transcriptional profiling of dissected genital imaginal discs of each sex at three time points during early morphogenesis. Using a stringent statistical threshold, we identified 23 genes that have sex-differential transcript levels at all three time points, of which 13 encode transcription factors, a significant enrichment. We focus here on three sex-specifically expressed transcription factors encoded by lozenge (lz), Drop (Dr) and AP-2. We show that, in female genital discs, Dsx activates lz and represses Dr and AP-2. We further show that the regulation of Dr by Dsx mediates the previously identified expression of the fibroblast growth factor Branchless in male genital discs. The phenotypes we observe upon loss of lz or Dr function in genital discs explain the presence or absence of particular structures in dsx mutant flies and thereby clarify previously puzzling observations. Our time course of expression data also lays the foundation for elucidating the regulatory networks downstream of the sex-specifically deployed transcription factors.