POSITIVE AND NEGATIVE SIGNALS FROM MESODERM REGULATE THE EXPRESSION OF MOUSE OTX2 IN ECTODERM EXPLANTS

Otx2, a mouse homolog of the Drosophila orthodenticle gene, is first w idely expressed in the epiblast but becomes progressively restricted t o the anterior third of the embryo by the headfold stage. This progres sive restriction correlates with the anterior migration of mesoderm in the embryo, suggesting that interactions with mesoderm may be involve d in setting up the anterior domain of Otx2 expression in vivo. Using explant-recombination assays, we have obtained evidence that a positiv e signal from anterior mesendoderm is required to stabilize expression of Otx2 in vivo, whereas a negative signal from the later-forming pos terior mesendoderm represses Otx2 expression in the posterior part of the embryo. We have also found that exogenous retinoic acid can mimic the effect of this negative signal and reduces the anterior domain of Otx2 expression.