Determination of embryonic polarity in a regulative system: evidence for endogenous inhibitors acting sequentially during primitive streak formation in the chick embryo

Avian embryos have a remarkable capacity to regulate: when a pre-primitive streak stage embryo is cut into fragments, each fragment can spontaneously initiate formation of a complete embryonic axis. We investigate the signalling pathways that initiate primitive streak formation and the mechanisms that ensure that only a single axis normally forms. As reported previously, an ectopic primitive streak can be induced by misexpression of Vg1 in the marginal zone. We now show that Vg1 induces an inhibitor that travels across the embryo (3 mm distance) in less than 6 hours. We provide evidence that this inhibitor acts early in the cascade of events downstream of Vg1. We also show that FGF signalling is required for primitive streak formation, in cooperation with Nodal and Chordin. We suggest that three sequential inhibitory steps ensure that a single axis develops in the normal embryo: an early inhibitor that spreads throughout the embryo (which can be induced by Vg1), a second inhibition by Cerberus from the underlying hypoblast, and finally a late inhibition from Lefty emitted by the primitive streak itself.