The investigator will generate and analyze hypomorphic, null and cell-specific gene modifications of Pitx2. Specific antibodies will be generated to assess the cell specificity of Pitx2 expression in the pituitary and other organs of intact animals. Several pituitary hormone genes have binding sites for Pitx2. There are three isoforms of Pitx2, two of which are expressed in the pituitary gland (Pitx2a, Pitx2b). The relative activity of each Pitx2 isoform on expression of known target genes will be assessed by transient transfection studies using homologous pituitary cell lines. The effects of ectopic Pitx2a and Pitx2b expression in pituitary corticotropes will also be investigated using both transient transfection and transgenic mice. By combining the approaches of transfection, embryonic stem cell technology mice, the investigator will dissect the contributions of individual cells and individual genes in regulating the normal growth and development of the pituitary.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD034283-04
Application #
2911491
Study Section
Endocrinology Study Section (END)
Program Officer
Javois, Lorette Claire
Project Start
1999-07-15
Project End
2004-06-30
Budget Start
1999-07-15
Budget End
2000-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Genetics
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Cheung, Leonard Y M; George, Akima S; McGee, Stacey R et al. (2018) Single-Cell RNA Sequencing Reveals Novel Markers of Male Pituitary Stem Cells and Hormone-Producing Cell Types. Endocrinology 159:3910-3924
Cheung, Leonard Y M; Okano, Hideyuki; Camper, Sally A (2017) Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes. Mol Cell Endocrinol 439:213-223
Cheung, Leonard Y M; Davis, Shannon W; Brinkmeier, Michelle L et al. (2017) Regulation of pituitary stem cells by epithelial to mesenchymal transition events and signaling pathways. Mol Cell Endocrinol 445:14-26
Gergics, Peter; Christian, Helen C; Choo, Monica S et al. (2016) Gene Expression in Mouse Thyrotrope Adenoma: Transcription Elongation Factor Stimulates Proliferation. Endocrinology 157:3631-46
Davis, Shannon W; Keisler, Jessica L; Pérez-Millán, María I et al. (2016) All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors. Endocrinology 157:1385-96
Fang, Qing; George, Akima S; Brinkmeier, Michelle L et al. (2016) Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era. Endocr Rev 37:636-675
Rubel, Cory A; Wu, San-Pin; Lin, Lin et al. (2016) A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function. Cell Rep 17:1414-1425
Pérez Millán, María Inés; Brinkmeier, Michelle L; Mortensen, Amanda H et al. (2016) PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells. Elife 5:
Davis, Shannon W; Mortensen, Amanda H; Keisler, Jessica L et al. (2016) ?-catenin is required in the neural crest and mesencephalon for pituitary gland organogenesis. BMC Dev Biol 16:16
Gergics, Peter; Brinkmeier, Michelle L; Camper, Sally A (2015) Lhx4 deficiency: increased cyclin-dependent kinase inhibitor expression and pituitary hypoplasia. Mol Endocrinol 29:597-612

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