Corticotroph ontogeny during vertebrate development involves molecular pathways distinct from other pituitary cell lineages. The critical determinants of corticotroph differentiation remain largely unclear. Both transcription factors and soluble molecules signaling via Jak/STAT pathways are involved in corticotroph development and pro-opiomelanocortin (POMC) expression. Using POMC expression as an entry point, I propose to study genetic and molecular mechanisms underlying corticotroph determination and differentiation in zebrafish.
The aims of this K08 proposal are (1) to elucidate the critical roles of STAT 3 in POMC lineage development; (2) to perform a genetic screen to identify and characterize essential genes required for development of POMC lineage. The latter aim will be achieved through participation in a NIH-funded organ-specific genetic screen that utilizes live transgenic zebrafish harboring fluorescent tissues. Transgenic zebrafish expressing green fluorescent protein driven by the POMC promoter offer a unique in vivo model allowing a detailed genetic analysis of POMC-specific cells in living embryos. As the candidate for this proposal, I am currently a fellow in the Division of Endocrinology, Cedars- Sinai Medical Center (CSMC), UCLA and will complete my fellowship in June 2003. Through the proposed studies, I will expand my knowledge of general and neuro- endocrinology, especially pituitary developmental biology, and further a broad training in molecular biology, genetics, embryology and endocrinology. By the end of this award, I will be eminently trained to undertake independent basic research in pituitary development and to pursue a productive research career in academic medicine. The faculty at CSMC and UCLA have excellent reputations in both strong basic research and training physicians to develop independent careers in academic medicine. I will be mentored by both endocrine and developmental biology faculty at CSMC and UCLA, which will provide synergistic enrichment for this K08 application. CSMC has well-established programs related to my proposal and research interests and is fully committed to sustain my research career development in an environment of academic excellence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK064806-02
Application #
6802301
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2003-09-30
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$123,552
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Liu, Ning-Ai; Jiang, Hong; Ben-Shlomo, Anat et al. (2011) Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor. Proc Natl Acad Sci U S A 108:8414-9
RĂ­os, Yesenia; Melmed, Shlomo; Lin, Shuo et al. (2011) Zebrafish usp39 mutation leads to rb1 mRNA splicing defect and pituitary lineage expansion. PLoS Genet 7:e1001271
Liu, Ning-Ai; Ren, Meina; Song, Jianbo et al. (2008) In vivo time-lapse imaging delineates the zebrafish pituitary proopiomelanocortin lineage boundary regulated by FGF3 signal. Dev Biol 319:192-200
Liu, Ning-Ai; Liu, Qian; Wawrowsky, Kolja et al. (2006) Prolactin receptor signaling mediates the osmotic response of embryonic zebrafish lactotrophs. Mol Endocrinol 20:871-80