Immunohistochemistry in the analysis of mouse aggregation chimaeras.

We have used cellular mosaicism in chimaeric mice to study the clonal organization of normal tissues. The mosaicism has been demonstrated in sections and in whole mounts of intestinal epithelium, aortic endothelium and retinal pigment epithelium using H2 antigens and a carbohydrate polymorphism recognized by Dolichos biflorus lectin as strain-specific markers. The results show that the epithelium of each adult intestinal crypt is derived from a single progenitor cell. Because crypts of differing genotype may contribute cells to the same villus, the pathways of cell migration up the villi can be demonstrated. The ability to stain mosaic patches in two dimensions in large intact sheets of epithelium has permitted a more satisfactory analysis in terms of clonal development than was previously possible with data from tissue sections. We have adapted statistical procedures from plant ecology to examine the scale of clustering of patches of like genotype, and thence to recognize 'descendent' clones, i.e. groups of cells which are not contiguous, but are related by descent from a common ancestor in embryogenesis.