Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis

SMAD2 is a member of the transforming growth factor beta and activin-signal ing pathway, To examine the role of Smad2 in postgastrulation development, we independently generated mice with a null mutation in this gene. Smad2-de ficient embryos die around day 7.5 of gestation because of failure of gastr ulation and failure to establish an anterior-posterior (A-P) axis. Expressi on of the homeobox gene Hex (the earliest known marker of the A-P polarity and the prospective head organizer) was found to be missing in Smad2-defici ent embryos. Homozygous mutant embryos and embryonic stem cells formed meso derm derivatives revealing that mesoderm induction is SMAD2 independent. In the presence of wild-type extraembryonic tissues, Smad2-deficient embryos developed beyond 7.5 and up to 10.5 days postcoitum, demonstrating a requir ement for SMAD2 in extraembryonic tissues for the generation of an A-P axis and gastrulation, The rescued postgastrulation embryos showed malformation of head structures, abnormal embryo turning, and cyclopia. Our results sho w that Smad2 expression is required at several stages during embryogenesis.