Implantation and ablation experiments which manipulated the notochord in both chick and mouse embryos [221, 284–287] verified that the notochord is required for formation of the MHP. It was proposed that the notochord releases a morphogen that may regulate MHP formation. Shh protein is expressed in the notochord at this stage [113, 288] and application of either Shh-expressing cells or purified protein to intermediate neural plate explants leads to induction of the floor plate , suggesting that Shh is the MHP-inducing morphogen. However, MHP formation is not totally abolished in Shh-null mouse embryos, suggesting that other factors from the notochord may also have MHP-inducing properties .