although the hypoblast does not contribute to the embryo, it has great influences on the orientation of the embryonic axis. for example, the ave in hypoblast plays an important role in positioning the primitive streak at the midland of the amniote embryos. in chick, people had observed that removal of the hypoblast caused multiple, ectopic primitive streaks formation. similarly, in mice embryo, the ave expresses secreted molecules, including two antagonists of nodal signaling, cerberus-like (cerl) and a tgfβ superfamily molecule, lefty1. it was shown that cerberus−/−;lefty1−/− compound mutants mice developed a primitive streak ectopically in the embryo. there is also finding suggested that the hypoblast also inhibit primitive streak formation by depositing extracellular matrix components to inhibit epithelial-mesenchymal transition (emt). besides the role of positioning the site of gastrulation, ave also showed other function including continued protection against caudalization of the early nervous system. also primitive endoderm derived yolk sac has major function in guaranteeing the proper organogenesis of the fetus and efficient exchange of nutrients, gases and wastes.