Reconciling different models of forebrain induction and patterning: a dualrole for the hypoblast

Several models have been proposed for the generation of the rostral nervous system. Among them, Nieuwkoop's activation/transformation hypothesis and S pemann's idea of separate head and trunk/tail organizers have been particul arly favoured recently. In the mouse, the finding that the visceral endoder m (VE) is required for forebrain development has been interpreted as suppor t for the latter model. Here we argue that the chick hypoblast is equivalen t to the mouse VE, based on fate, expression of molecular markers and chara cteristic anterior movements around the time of gastrulation, We show that the hypoblast does not fit the criteria for a head organizer because it doe s not induce neural tissue from naive epiblast, nor can it change the regio nal identity of neural tissue. However, the hypoblast does induce transient expression of the early markers Sox3 and Otx2. The spreading of the hypobl ast also directs cell movements in the adjacent epiblast, such that the pro spective forebrain is kept at a distance from the organizer at the tip of t he primitive streak. We propose that this movement is important to protect the forebrain from the caudalizing influence of the organizer. This dual ro le of the hypoblast is more consistent with the Nieuwkoop model than with t he notion of separate organizers, and accommodates the available data from mouse and other vertebrates.