Complete dissipation of coherent clonal growth occurs before gastrulation in mouse epiblast

Observations on chimaeric mice argue that there must be considerable dispersal and intermingling of the clonal descendants of epiblast founder cells at an early stage in the development of the tissue. However, it has not been established when or how this occurs. Here we have used a genetic marker that enables donor cells to be visualized in situ to examine the early postimplantation distribution of clones obtained by transplanting epiblast founder cells into host blastocysts. We have also determined the spatial relationship between sister cells in non-chimaeric postimplantation epiblast by ionophoretic injection of a fluorescent macromolecule. Both experimental approaches support the conclusion that breakdown of coherent clonal growth accompanies epithelialization of the epiblast and is essentially complete by the onset of gastrulation. Furthermore, the clonal analysis shows that descendants of different epiblast founder cells continue to intermingle extensively well into organogenesis. We suggest that this sustained intermingling of cells in the epithelial epiblast, which does not occur in the adjacent visceral endoderm, depends on cells losing contact with the basal lamina when they divide. These findings have implications both for patterning of the early amniote embryo and for the growth of tall columnar epithelia in general.