Investigation of Cellular Interaction and Deployment in the Early Mammalian Embryo Using Interspecific Chimaeras between the Rat and Mouse

Mammalian chimaeras can be produced experimentally by aggregating early embryos or by injecting cells into them. They have been used to study several aspects of early development. However, lack of a genetic marker enabling unequivocal identification of all cells of either genotype in situ has frustrated full exploitation of the experimental possibilities offered by these organisms. Hence interspecific chimaeras have been produced between rat and mouse embryos in which cells of the two species can be identified in sectioned embryos by immune fluorescence. These chimaeric embryos have been used to study differentiation of the trophoblast and inner cell mass, and the deployment of cells during morphogenesis. Preliminary results suggest that the two tissues are determined by the blastocyst stage, and that the trophoblast forms part of the extra-embryonic membranes originally presumed to be derived from the inner cell mass. Also, rat inner cell mass cells can induce mitosis in mouse trophoblast. Futhermore, the distribution of rat cells in implanted embryos suggests that the embryo may grow in a coherent clonal manner from a very early stage. Very recently, chimaerism has been induced by transplanting single rat cells, which may allow a more critical analysis of morphogenesis and determination than was possible hitherto. An obvious question raised by crossing the species barrier is the extent to which results may be applicable to normal development. Adverse effects of immunological interaction between the mouse uterine foster-mother and fetal rat cells, and sorting out of cells according to species, are two of the problems that might complicate interpretation of these experiments.