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REGULATION OF LUNG EPITHELIAL DIFFERENTIATION ALVEOLARIZATION AND GENE EXPRESSION BY GATA-6 IN VITRO AND IN VIVO

LIU, CONG
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026498687

Abstract Details

2002, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Zinc finger containing GATA family transcription factors have been shown to regulate cell lineage specific gene expression and differentiation in many organs. GATA-6 is the only family member that is expressed in endodermally derived pulmonary epithelium where GATA-6 influences the expression of surfactant protein A, C (SP-A, C) and thyroid transcription factor I (TTF-1). In the first part of the present study, we tested the hypothesis that precisely regulated expression of GATA-6 in respiratory epithelium is required for epithelial differentiation and alveolarization. Transgenic mice expressing a dominant negative form of GATA-6, GATA-6-engrailed fusion protein, were generated using a doxycycline inducible expression system. This loss of function assay demonstrated that GATA-6 was required for the maturation of respiratory epithelium in late gestation as shown by delayed morphogenesis and down-regulated differentiation markers of Type I, Type II epithelial cells and Clara cells. Transgenic mice expressing GATA-6 after E18.5, when endogenous GATA-6 expression decreased, were generated using the human SP-C promoter. This gain of function assay demonstrated that down-regulation of endogenous GATA-6 during postnatal period is required for the alveolarization process as shown by defects in septation and emphysema developed in the GATA-6 transgenic mice. In the second part of the thesis, we investigated the molecular mechanisms by which GATA-6 regulates the lung specific SP-C gene promoter. Our results showed that GATA-6 directly interacted with TTF-1 and that these interactions contributed to the synergistic effects of GATA-6 and TTF-1 on the SP-C promoter. Therefore both in vivo and in vitro studies indicated that GATA-6 regulates epithelial differentiation, alveolarization and gene expression in the lung.
Dr. Jeffrey A. Whitsett (Advisor)
1 p.
GATA-6; lung development; transcription factor; gene regulation

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Citations

  • LIU, C. (2002). REGULATION OF LUNG EPITHELIAL DIFFERENTIATION ALVEOLARIZATION AND GENE EXPRESSION BY GATA-6 IN VITRO AND IN VIVO [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026498687

    APA Style (7th edition)

  • LIU, CONG. REGULATION OF LUNG EPITHELIAL DIFFERENTIATION ALVEOLARIZATION AND GENE EXPRESSION BY GATA-6 IN VITRO AND IN VIVO. 2002. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026498687.

    MLA Style (8th edition)

  • LIU, CONG. "REGULATION OF LUNG EPITHELIAL DIFFERENTIATION ALVEOLARIZATION AND GENE EXPRESSION BY GATA-6 IN VITRO AND IN VIVO." Doctoral dissertation, University of Cincinnati, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026498687

    Chicago Manual of Style (17th edition)

ucin1026498687
© 2002, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.