Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
G3 (Bethesda). 2021 Aug 7;11(8). doi: 10.1093/g3journal/jkab172.
The mechanisms that determine the final topology of skeletal muscles remain largely unknown. We have been developing Drosophila body wall musculature as a model to identify and characterize the pathways that control muscle size, shape, and orientation during embryogenesis. Our working model argues muscle morphogenesis is regulated by (1) extracellular guidance cues that direct muscle cells toward muscle attachment sites, and (2) contact-dependent interactions between muscles and tendon cells. While we have identified several pathways that regulate muscle morphogenesis, our understanding is far from complete. Here, we report the results of a recent EMS-based forward genetic screen that identified a myriad of loci not previously associated with muscle morphogenesis. We recovered new alleles of known muscle morphogenesis genes, including back seat driver, kon-tiki, thisbe, and tumbleweed, arguing our screen had the depth and precision to uncover myogenic genes. We also identified new alleles of spalt-major, barren, and patched that presumably disrupt independent muscle morphogenesis pathways. Equally as important, our screen shows that at least 11 morphogenetic loci remain to be mapped and characterized. Our screen has developed exciting new tools to study muscle morphogenesis, which may provide future insights into the mechanisms that regulate skeletal muscle topology.
骨骼肌最终拓扑结构的决定机制在很大程度上仍然未知。我们一直在开发果蝇体壁肌肉组织作为模型,以鉴定和描述控制胚胎发生过程中肌肉大小、形状和方向的途径。我们的工作模型认为肌肉形态发生受(1)指导肌肉细胞向肌肉附着点的细胞外导向线索,以及(2)肌肉和肌腱细胞之间的接触依赖性相互作用调节。虽然我们已经确定了几个调节肌肉形态发生的途径,但我们的理解还远远不够。在这里,我们报告了最近基于 EMS 的正向遗传筛选的结果,该筛选鉴定出了以前与肌肉形态发生无关的无数基因座。我们回收了已知肌肉形态发生基因的新等位基因,包括 back seat driver、kon-tiki、thisbe 和 tumbleweed,这表明我们的筛选具有足够的深度和精度来揭示肌源性基因。我们还鉴定了 spalt-major、barren 和 patched 的新等位基因,这些基因可能破坏了独立的肌肉形态发生途径。同样重要的是,我们的筛选表明,至少有 11 个形态发生基因座有待绘制和表征。我们的筛选为研究肌肉形态发生提供了令人兴奋的新工具,这可能为调节骨骼肌肉拓扑结构的机制提供未来的见解。