Variability of chimaeras and mosaics

Abstract

Aggregation chimaeras and X-inactivation mosaics in mice are alike in general appearance, but chimaeras are very much more variable in the proportions of the cell types (p) seen for example in coat pigmentation. The distribution of p in chimaeras is not binomial, but is uniform, or flat, between the two extremes. The greater variability of chimaeras arises from two sampling events that occur when cellular heterogeneity is already present in chimaeras but before it arises in mosaics. These are the differentiation of the inner cell mass from the trophectoderm and of the primary ectoderm from the primary endoderm. The second of these generates the flat distribution of chimaeras as a consequence of the two cell types being unmixed at that time. The two sampling events generate single-colour individuals in roughly the proportions observed. Consideration of the second sampling event provides evidence that the primordial germ cells must originate in the primary ectoderm and not in the yolk-sac. Estimation of numbers of progenitor cells on the supposition of binomial sampling is not valid unless the clone-size is known or the cells in the sample are not contiguous. Data on coat pigmentation are consistent with the assumptions that X-inactivation is random in about 21 cells, that the sampling of melanoblasts is binomial (because they are not contiguous), and that the melanocytes of the head and body are descended from about 34 progenitor cells.