Lee Tzumin
Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA, USA.
Wiley Interdiscip Rev Dev Biol. 2014 Jan-Feb;3(1):69-81. doi: 10.1002/wdev.122. Epub 2013 Jun 28.
By generating and studying mosaic organisms, we are learning how intricate tissues form as cells proliferate and diversify through organism development. FLP/FRT-mediated site-specific mitotic recombination permits the generation of mosaic flies with efficiency and control. With heat-inducible or tissue-specific FLP transgenes at our disposal, we can engineer mosaics carrying clones of homozygous cells that come from specific pools of heterozygous precursors. This permits detailed cell lineage analysis followed by mosaic analysis of gene functions in the underlying developmental processes. Expression of transgenes (e.g., reporters) only in the homozygous cells enables mosaic analysis in the complex nervous system. Tracing neuronal lineages by using mosaics revolutionized mechanistic studies of neuronal diversification and differentiation, exemplifying the power of genetic mosaics in developmental biology.
通过生成和研究嵌合体生物,我们正在了解复杂的组织如何在生物体发育过程中随着细胞增殖和多样化而形成。FLP/FRT介导的位点特异性有丝分裂重组能够高效且可控地生成嵌合体果蝇。利用可热诱导或组织特异性表达的FLP转基因,我们能够构建出带有纯合细胞克隆的嵌合体,这些纯合细胞来源于特定的杂合前体细胞库。这使得我们能够进行详细的细胞谱系分析,随后对基础发育过程中的基因功能进行嵌合体分析。仅在纯合细胞中表达转基因(例如报告基因),能够在复杂的神经系统中进行嵌合体分析。利用嵌合体追踪神经元谱系彻底改变了神经元多样化和分化的机制研究,例证了遗传嵌合体在发育生物学中的强大作用。