Tracking of mouse cell lineage using microinjected DNA sequences: analyses using genomic Southern blotting and tissue-section in situ hybridizations.

We examined the feasibility of applying DNA microinjection to label cells for lineage studies of mouse embryos. Tissues from three transgenic mice mosaic due to the insertion of an exogenously introduced mouse beta-major globin gene were analyzed by genomic Southern-blotting and in situ hybridization. These studies allowed the direct quantification and localization of lineage descendants derived from the marked or transformed founder cells. The results of these studies suggested an early segregation of cells in the somatic vs. germ-cell lineages. The in situ hybridization data further demonstrated that cells of the transformed lineages were usually finely dispersed, indicative of extensive cell-cell mixing during mouse development. However, a notable exception to this was the patchy distribution of cells in the kidney (corresponding to individual nephrons), the clustering of transformed cells in individual villi of the small intestine, and the segregation of positive and negative seminiferous tubules in the testis. These data suggest a clonal basis for the organization of development in organs like the kidney, intestine, and testis.