Jensen Patricia, Dymecki Susan M
Laboratory of Neurobiology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC, USA.
Methods Mol Biol. 2014;1092:437-54. doi: 10.1007/978-1-60327-292-6_26.
Fate maps, by defining the relationship between embryonic tissue organization and postnatal tissue structure, are one of the most important tools on hand to developmental biologists. In the past, generating such maps in mice was hindered by their in utero development limiting the physical access required for traditional methods involving tracer injection or cell transplantation. No longer is physical access a requirement. Innovations over the past decade have led to genetic techniques that offer means to "deliver" cell lineage tracers noninvasively. Such "genetic fate mapping" approaches employ transgenic strategies to express genetically encoded site-specific recombinases in a cell type-specific manner to switch on expression of a cell-heritable reporter transgene as lineage tracer. The behaviors and fate of marked cells and their progeny can then be explored and their contributions to different tissues examined. Here, we review the basic concepts of genetic fate mapping and consider the strengths and limitations for their application. We also explore two refinements of this approach that lend improved spatial and temporal resolution: (1) Intersectional and subtractive genetic fate mapping and (2) Genetic inducible fate mapping.
命运图谱通过定义胚胎组织结构与出生后组织结构之间的关系，成为发育生物学家手中最重要的工具之一。过去，在小鼠中绘制此类图谱受到其子宫内发育的限制，这限制了涉及示踪剂注射或细胞移植的传统方法所需的物理操作。现在不再需要物理操作。过去十年的创新带来了基因技术，这些技术提供了以非侵入性方式“传递”细胞谱系示踪剂的方法。这种“基因命运图谱”方法采用转基因策略，以细胞类型特异性方式表达基因编码的位点特异性重组酶，从而开启作为谱系示踪剂的细胞可遗传报告转基因的表达。然后可以探索标记细胞及其后代的行为和命运，并检查它们对不同组织的贡献。在这里，我们回顾基因命运图谱的基本概念，并考虑其应用的优势和局限性。我们还探讨了这种方法的两种改进，它们提高了空间和时间分辨率：（1）交叉和减法基因命运图谱，以及（2）基因诱导命运图谱。
