The debate over the mechanisms involved in neural patterning has deep roots and two early models still have a strong heuristic influence. On the one hand, Spemann and his followers proposed the existence of separate organizers for the head and for the trunk/tail. On the other hand, Nieuwkoop suggested an early signal for the acquisition of an anterior fate and a subsequent transforming signal that specified posterior regions. Most of the recent evidence obtained in mammals has favoured the existence of two organizers. However, as Foley et al. argue in Development, this might not be the case and a modification of Nieuwkoop's hypothesis could be enough to explain how the induction of rostral structures occurs.

In mammals, the anterior visceral endoderm has been proposed as the presumptive head organizer. On the basis of an analysis of marker expression, Foley et al. identified the hypoblast as the equivalent structure in the chick, a finding consistent with early rotation experiments, which revealed an effect of the hypoblast on axial patterning. However, the authors found that grafting the hypoblast in an ectopic location did not induce brain tissue but only a transient expression of neural and forebrain markers, arguing against its role as a head organizer. Moreover, they found that the distortion observed in the rotation experiments could be explained by an effect of the hypoblast not on cell fate, but on cell movements in the epiblast.

The authors propose that early inductive signals lead to the unstable expression of forebrain markers, which acquire a stable character later in development. However, for this event to occur, the prospective forebrain needs to be protected from the posteriorizing influence of the organizer. Foley et al. argue that the movements governed by the hypoblast contribute to this protection by maintaining a safe distance between the future forebrain and the organizer. Later, other signals stabilize the anterior fate of those cells and continue to protect them from caudalization. This model, which can explain observations from chick and mouse, bears more resemblance to Nieuwkoop's idea than to the proposal for the existence of two organizers. These findings should lead us to explore whether the mammalian anterior visceral endoderm can also affect cell movements and the nature of the hypoblast-derived signals involved in this phenomenon.