Appropriate development of the pituitary gland during embryogenesis involves a complex interplay between the developing gland and adjacent tissues. In addition, precise transcriptional control within the pituitary is critical to the determination and differentiation of cellular lineages in the correct temporal and spatial patterns as the gland matures. Aberrant control of target gene expression by transcriptional regulators within the pituitary can result in improper pituitary formation. A complete characterization, therefore, of the inductive extrinsic and intrinsic pathways governing pituitary development during embryogenesis is crucial to the identification of therapeutic targets and eventually therapies for human growth disorders.
The specific aims for this study are: to characterize the inductive regulation of known anterior pituitary-specific transcription factors mediated by extrinsic neuroepithelial signaling molecules, to discern the combinatorial genetic interactions between known dorsal factors governing Pit-I expression and to elucidate and critically define the regulatory elements of FGF8 required for ventral diencephalon/infundibulum expression. Coculture explant assays will be performed utilizing tissues from the pituitary in combination with adjacent areas such as the neuroepithelia or cell lines modified to express candidate inducing factors. As well, transgenic promoter characterization will be conducted for neuroepithelial signaling molecules such as FGF8 hypothesized to induce differentiation of the dorsal pituitary cell types and transcription factors thought to play roles in pituitary development. These studies should define extrinsic and intrinsic pituitary mechanisms regulating the formation of the gland.
