Investigation of early mammalian development using interspecific chimaeras between rat and mouse.

Abstract

THE analysis of genetic mosaics has allowed inferences to be made about several otherwise elusive aspects of development including cell determination, division rates, lineage and deployment and the sizes of pools of precursor cells destined to form particular organs and tissues. The most significant results have been achieved using insect mosaics arising in early development from spontaneous or induced genetic modification of one cell1, 2. Extensive genetic mosaicism may also occur in mammals either arising spontaneously during development as a result of random × chromosome inactivation in female embryos3 or by the experimental combination of embryos of different genotype to form chimaeras4–6. Human or mouse mosaics carrying enzymic, chromosomal or pigmentation markers have been used in several investigations into cell lineage and the size of precursor pools of cells. Use of these markers often, however, involves analysis long after the critical developmental events have taken place and so the results are likely to be distorted by differential proliferation, migration and death of cells. Furthermore. many of the available markers have only a limited tissue distribution and, with the exception of those involving pigmentation, differentiation of photoreceptors and isoenzymes of β-glucuronidase7–9, only yield estimates of the ratio of cells in mosaic tissues and provide no information about their spatial arrangement. Therefore some of the conclusions drawn from analyses of mammalian mosaics have been based on assumptions of questionable validity10–13.