Nucleotide exchange factor RIC-8 is indispensable in mammalian early development.

The guanine nucleotide exchange factor RIC-8 is a conserved protein essential for the asymmetric division in the early embryogenesis in different organisms. The function of RIC-8 in mammalian development is not characterized so far. In this study we map the expression of RIC-8 during the early development of mouse. To elucidate the RIC-8 function we used Ric-8(-/-) mutant embryos. The Ric-8(-/-) embryos reach the gastrulation stage but do not develop further and die at E6.5-E8.5. We characterized the Ric-8(-/-) embryonic phenotype by morphological and marker gene analyses. The gastrulation is initiated in Ric-8(-/-) embryos but their growth is retarded, epiblast and mesoderm disorganized. Additionally, the basement membrane is defective, amnion folding and the formation of allantois are interfered, also the cavitation. Furthermore, the orientation of the Ric-8(-/-) embryo in the uterus was abnormal. Our study reveals that the activity of RIC-8 protein is irreplaceable for the correct gastrulation of mouse embryo.