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Role of Prop1 in pituitary development

Sean X. Li

Appointment Period: 1998-1999 / Grant Year: [13]

The crucial physiological function including homeostasis, reproduction and survival of vertebrate organisms requires precise regulation of the endocrine system, which is controlled by the hypothalamic-pituitary axis. The anteriorpituitary gland receives and integrates information from the brain via the hypothalamus, and signals peripheral endocrine organs such as the thyroid, adrenal gland and gonads. During early embryogenesis, primordial of the anterior pituitary, Rathke's pouch, is induced by contact-dependent interaction of the ventral diencephalon. Subsequently, the anterior pituitary differentiates into five independent endocrine cell types in a spatial and temporal specific manner. Understanding the molecular mechanism governing the formation of individual cell types in the pituitary gland was the main focus of my research. Recently, families of transcription factors have been identified and demonstrated to be important for pituitary development. These include Pit-1, Prop-1, P-lim, P-otx-1/2 and Brn 4.0. However, the mechanism of how the combinatorial interactions of these factors that dictate the cell type specificity still remains unclear. In an attempt to address this issue, I employed mouse genetic approaches including both loss-of-function and gain-of-function techniques to pinpoint the functional role of these genes in pituitary cell determination. In addition, the latest tissue-specific gene targeting technology has been used to delete genes specifically in the pituitary sothat we can delinearize the gene's specific function in the pituitary gland. This technology requires generation of a special stain of mouse which expresses Cre protein, a novel site-specific recombinase.

PUBLICATIONS (resulting from this training, and some recent ones)

Li X, Perissi V, Liu F, Rose DW, Rosenfeld MG. (2002) Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science 297:1180-3.

Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, Nigam SK, Aggarwal AK, Maas R, Rose DW, Rosenfeld MG. (2003) Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature 426:247-54.

Li X, Rosenfeld MG. (2004) Transcription: origins of licensing control. Nature 427:687-8.

Cai CL, Zhou W, Yang L, Bu L, Qyang Y, Zhang X, Li X, Rosenfeld MG, Chen J, Evans S. (2005) T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis. Development 132:2475-87.

Olson LE, Tollkuhn J, Scafoglio C, Krones A, Zhang J, Ohgi KA, Wu W, Taketo MM, Kemler R, Grosschedl R, Rose D, Li X, Rosenfeld MG. (2006) Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell 125:593-605.

Bush KT, Vaughn DA, Li X, Rosenfeld MG, Rose DW, Mendoza SA, Nigam SK. (2006) Development and differentiation of the ureteric bud into the ureter in the absence of a kidney collecting system. Dev Biol. 298:571-84.