Interaction between Otx2 and Gbx2 defines the organizing center for the optic tectum

Otx2 is expressed in the mesencephalon and prosencephalon, and Gbx2 is expr essed in the rhombencephalon around stage 10. Loss-of-function studies of t hese genes in mice have revealed that Otx2 is indispensable for the develop ment of the anterior brain segment, and that Gbx2 is required for the devel opment of the isthmus. We carried out gain-of-function experiments of these genes in chick embryos with a newly developed gene transfer system, in ovo electroporation. When Otx2 was ectopically expressed caudally beyond the m idbrain-hindbrain boundary (MHB), the alar plate of the metencephalon diffe rentiated into the optic tectum instead of differentiating into the cerebel lum. On the other hand, when Gbx2 was ectopically expressed at the mesencep halon, the caudal limit of the tectum shifted rostrally. We looked at the e ffects of misexpression on the isthmus- and tectum-related molecules. Otx2 and Gbx2 interacted to repress each other's expression. Ectopic Otx2 and Gb x2 repressed endogenous expression of Fgf8 in the isthmus, but induced Fgf8 expression at the interface between Otx2 and Gbx2 expression. Thus, it is suggested that interaction between Otx2 and Gbx2 determines the site of Fgf 8 expression and the posterior limit of the tectum. (C) 2000 Elsevier Scien ce Ireland Ltd. All rights reserved.