The anterior pituitary gland provides a powerful model system in which to study the molecular mechanisms by which specific cell types emerge from a common primordium. Multiple signaling events have proven critical for the determination of the seven distinct pituitary cell phenotypes, and the actions of opposing FGF8 and BMP2 gradients appear to establish overlapping patterns of expression of a series of tissue-specific or tissue-restricted transcription factors. Two of the most ventral factors during pituitary ontogeny, a novel forkhead protein, P-Frk and GATA2, are of specific interest with respect to their potential role in ventral cell type development.
The Specific Aims of my proposal are to examine in vivo and in vitro the role of P-Frk in pituitary development and cell-type specification, and to examine regulation of P-Frk by BMP2, Shh and FGF8. Further, I will explore whether P-Frk and GATA 2 function synergistically and/or have an epistatic relationship in determining ventral cell (gonadotrope, thyrotrope) phenotypes. Experiments will involve both organ co-culture assays as well as a variety of in vivo approaches, which should provide specific information, as well as training in the use of molecular biological approaches to the study of development of the neuroendocrine system.
| Zhu, Xiaoyan; Zhang, Jie; Tollkuhn, Jessica et al. (2006) Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis. Genes Dev 20:2739-53 |
