The Type II Activin Receptors Are Essential for Egg Cylinder Growth, Gastrulation, and Rostral Head Development in Mice

Abstract

The type II activin receptors, ActRIIA and ActRIIB, have been shown to play critical roles in axial patterning and organ development in mice. To investigate whether their function is required for mesoderm formation and gastrulation as implicated in Xenopus studies, we generated mice carrying both receptor mutations by interbreeding the ActRIIA and ActRIIB knockout mutants. We found that embryos homozygous for both receptor mutations were growth arrested at the egg cylinder stage and did not form mesoderm. Further analyses revealed that ActRIIA−/−ActRIIB+/− and about 15% of the ActRIIA−/− embryos failed to form an elongated primitive streak, resulting in severe disruption of mesoderm formation in the embryo proper. Interestingly, we observed similar gastrulation defects in ActRIIA−/−nodal+/− double mutants, which, if they developed beyond the gastrulation stage, displayed rostral head defects and cyclopia. These results provide genetic evidence that type II activin receptors are required for egg cylinder growth, primitive streak formation, and rostral head development in mice.