The role of Grainy head in epithelial tissue growth

• Author(s): Ponte, Susana Isabel Pereira da
• Date: 2014
• Persistent ID: http://hdl.handle.net/10362/13839
• Origin: Repositório Institucional da UNL
• Subject(s): Grainy head; Epithelia; Growth; Drosophila; Wing; Wing imaginal disc
• Document Type: Master thesis
• Language: English
• Advisor(s): Carvalho, Lara
• Contributor(s): RUN

Description

Part of the results of this thesis was presented in the following meetings: Susana Ponte, Lara Carvalho, Inês Cristo and António Jacinto. The role of Grainy head in epithelial tissue growth. Drostuga 2013. Faro, Portugal, January 3rd 2014 [poster] Susana Ponte, Lara Carvalho, Inês Cristo and António Jacinto. The role of Grainy head in epithelial tissue growth. Drostuga 2014. Tomar, Portugal, September 5th-6th 2014 [poster]

The grainy head (grh) gene family encodes an important group of transcription factors that play a remarkably conserved role in epithelial organ development, epithelial barrier formation and epithelial repair upon damage in different organisms. The regulation and molecular targets of Grh are numerous and seem to highly depend on the studied developmental context and tissue. Notably, the grh vertebrate homologs, called grh-like (grhl) genes, have recently been implicated in the pathogenesis of several human diseases, including tumor progression and metastasis in different types of cancer. However, the molecular mechanisms by which Grh exerts its function remain largely unknown. The main goal of this project was to investigate the role of Grh in epithelial growth and maintenance using the Drosophila melanogaster (fruit-fly) wing as an in vivo model system. We wanted to understand how Grh influences cell proliferation and apoptosis, as well as cell polarity, cell adhesion and cytoskeleton. Our results show that Grh is essential for epithelial cell survival, since both grh knockdown and overexpression lead to apoptosis. In addition, while grh knockdown induces an increase in cell proliferation, grh overexpression leads to the opposite phenotype, leading us to propose that this gene has a role in the control of cell proliferation. Grh seems to regulate both the expression and the localization of the cell adhesion protein E-cadherin in the wing disc epithelium. We also observed increased F-actin levels upon grh knockdown, suggesting that Grh can influence actin expression or dynamics. In conclusion, our data suggest that Grh is a key transcription factor in the regulation of epithelial maintenance and integrity of the Drosophila wing imaginal disc.