A novel inducible element, activated by contact with Rathke's pouch, is present in the regulatory region of the Rpx/Hesx1 homeobox gene.

Reciprocal inductive interactions are postulated to play a role in the determination and differentiation of the pituitary gland and the ventral hypothalamus. The homeobox gene Rpx/Hesxl is expressed during gastrulation in the anterior endoderm, prechordal plate, and the prospective cephalic neural plate, and at later stages of development in Rathke's pouch, the primordium of the pituitary. We have defined the regulatory elements necessary for proper spatial and temporal expression during development in transgenic mice using lacZ reporter genes. Proper spatial and temporal expression in the anterior endoderm prechordal plate and anterior neural plate can be recapitulated with as little as 568 bp of upstream sequence and intragenic sequence containing the first exon and intron. Late-stage expression in Rathke's pouch requires additional negative and positive regulatory elements. Interestingly, deletion analysis uncovered an element that directs transgene expression to a region of the hypothalamus that lies in direct contact with Rathke's pouch. In vitro tissue recombination experiments have established that this expression is induced by contact with the pouch. We propose that this element may be present in other genes that normally respond to signals emanating from the pouch during the development of the hypothalamic-pituitary axis. The Rpx-lacZ transgenic mice provide a novel model system for the molecular dissection of inductive cell signaling during pituitary development.