Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Department of Neurology, McKnight Brain Institute, University of Florida, 1149 Newell Drive, FL 32611, USA.
Development. 2018 Apr 25;145(8):dev163394. doi: 10.1242/dev.163394.
The ovary serves as a model for pioneering studies of stem cell niches, with defined cell types and signaling pathways supporting both germline and somatic stem cells. The establishment of the niche units begins during larval stages with the formation of terminal filament-cap structures; however, the genetics underlying their development remains largely unknown. Here, we show that the transcription factor Lmx1a is required for ovary morphogenesis. We found that Lmx1a is expressed in early ovarian somatic lineages and becomes progressively restricted to terminal filaments and cap cells. We show that Lmx1a is required for the formation of terminal filaments, during the larval-pupal transition. Finally, our data demonstrate that Lmx1a functions genetically downstream of Bric-à-Brac, and is crucial for the expression of key components of several conserved pathways essential to ovarian stem cell niche development. Importantly, expression of chicken Lmx1b is sufficient to rescue the null Lmx1a phenotype, indicating functional conservation across the animal kingdom. These results significantly expand our understanding of the mechanisms controlling stem cell niche development in the fly ovary.
卵巢是干细胞生态位开拓性研究的模型,其中定义明确的细胞类型和信号通路支持生殖细胞和体干细胞。生态位单位的建立始于幼虫阶段,形成终端丝-帽结构;然而,其发育的遗传基础在很大程度上仍然未知。在这里,我们表明转录因子 Lmx1a 是卵巢形态发生所必需的。我们发现 Lmx1a 在早期卵巢体谱系中表达,并逐渐局限于终端丝和帽细胞。我们表明 Lmx1a 在幼虫-蛹转变期间形成终端丝是必需的。最后,我们的数据表明 Lmx1a 在遗传上位于 Bric-à-Brac 下游,对于几个保守途径的关键组成部分的表达至关重要,这些途径对于卵巢干细胞生态位发育至关重要。重要的是,鸡 Lmx1b 的表达足以挽救 Lmx1a 缺失表型,表明在动物界具有功能保守性。这些结果大大扩展了我们对控制果蝇卵巢干细胞生态位发育的机制的理解。