The role of Sox2/SOX2 in hypothalamo-pituitary development. (360G-Wellcome-086545_Z_08_Z)

The overall aim of this project is to understand better the role of the transcription factor SOX2 in normal hypothalamo-pituitary development and in the pathogenesis of hypopituitarism in humans. Recently, we have identified a critical role for the transcription factor SOX2 in normal hypothalamo-pituitary development in both mice and humans; however, the molecular mechanism by which SOX2 dictates hypothalamo-pituitary development, namely its target genes and partner proteins, remains unknown. Th e main aims of the proposed research are: 1. To evaluate the ability of SOX2 to directly regulate specific genes known to be involved in forebrain and hypothalamo-pituitary development, and to identify the positions of these genes in the genetic hierarchy leading to normal pituitary development. 2. Identification of novel SOX2 target genes likely to be important in hypothalamo-pituitary development. 3. To investigate suitable co-operative partner factors for SOX2 in the developing pitu itary and their co-expression in human embryos. 4. Selection of candidates for mutation analysis of novel SOX2 target genes in patients with hypopituitarism and associated defects.