Institute for Neurosciences of Montpellier (INM), Univ Montpellier, INSERM, Montpellier, France.
Cell Mol Life Sci. 2022 Feb 20;79(3):141. doi: 10.1007/s00018-021-04077-1.
Understanding the generation of complexity in living organisms requires the use of lineage tracing tools at a multicellular scale. In this review, we describe the different multicolor strategies focusing on mouse models expressing several fluorescent reporter proteins, generated by classical (MADM, Brainbow and its multiple derivatives) or acute (StarTrack, CLoNe, MAGIC Markers, iOn, viral vectors) transgenesis. After detailing the multi-reporter genetic strategies that serve as a basis for the establishment of these multicolor mouse models, we briefly mention other animal and cellular models (zebrafish, chicken, drosophila, iPSC) that also rely on these constructs. Then, we highlight practical applications of multicolor mouse models to better understand organogenesis at single progenitor scale (clonal analyses) in the brain and briefly in several other tissues (intestine, skin, vascular, hematopoietic and immune systems). In addition, we detail the critical contribution of multicolor fate mapping strategies in apprehending the fine cellular choreography underlying tissue morphogenesis in several models with a particular focus on brain cytoarchitecture in health and diseases. Finally, we present the latest technological advances in multichannel and in-depth imaging, and automated analyses that enable to better exploit the large amount of data generated from multicolored tissues.
理解生命体复杂性的产生需要在多细胞尺度上使用谱系追踪工具。在这篇综述中,我们描述了不同的多色策略,重点介绍了在小鼠模型中表达几种荧光报告蛋白的方法,这些方法是通过经典(MADM、Brainbow 及其多个衍生工具)或急性(StarTrack、CLoNe、MAGIC Markers、iOn、病毒载体)转基因技术生成的。在详细描述了作为这些多色小鼠模型建立基础的多报告基因策略之后,我们简要提到了其他动物和细胞模型(斑马鱼、鸡、果蝇、iPSC),这些模型也依赖于这些构建体。然后,我们强调了多色小鼠模型在单细胞水平上更好地理解器官发生(克隆分析)的实际应用,以及在其他几个组织(肠道、皮肤、血管、造血和免疫系统)中的简要应用。此外,我们详细介绍了多色命运映射策略在理解几种模型中组织形态发生背后的精细细胞舞蹈的关键贡献,特别是在健康和疾病中的大脑细胞结构。最后,我们介绍了多通道和深度成像以及自动化分析方面的最新技术进步,这些进步使我们能够更好地利用多色组织产生的大量数据。