The hypothalamic-pituitary axis influences multiple bodily functions, such as homeostasis, growth, and reproduction. The concerted development of the primordia of the hypothalamus and pituitary (Rathke's pouch) during early embryogenesis presages the integrated neuroendocrine functions these tissues later share. Studies on the homeobox gene Rpx/HesxI have allowed unique molecular access to these early developmental processes. Rpx/HesxI is one of the earliest markers for the anterior region of the mouse embryo, and it is dynamically and transiently expressed in the prechordal plate, anterior forebrain and, at later stages of development, in Rathke's pouch. Targeted mutagenesis has demonstrated that Rpx plays a key role in the development of both the forebrain and the pituitary. In addition, examination of Rpx expression in other mouse pituitary mutants has allowed Rpx and other homeobox genes to be ordered in a putative regulatory hierarchy controlling pituitary organogenesis. It has been determined that multiple regulatory elements interdigitated within the Rpx gene separately control the early expression in the anterior forebrain and the late expression in Rathke's pouch in the mouse embryo. Dr. Mahon will undertake a further, more precise, delineation of the regulatory regions, focusing on sequences that are both structurally and functionally conserved between mouse and frog. Furthermore, based on the deletion analysis in frog and mouse, it will be possible to determine whether genes known to genetically regulate Rpx bind directly to Rpx regulatory sequences. This approach will further elaborate the genetic network involved in forebrain and pituitary development, and provide insight into the development of this important neuroendocrine system.
