2009 Fiscal Year Final Research Report

Role of TEAD1 in the proliferation of retinal pigment epithelial cells

Research Project

Project/Area Number	20791261
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Ophthalmology
Research Institution	Kumamoto University
Principal Investigator	KITAGAWA Michinori Kumamoto University, 発生医学研究所, 助教 (30314496)
Project Period (FY)	2008 – 2009
Keywords	眼発生 / 再生医学
Research Abstract	The TEAD family of transcription factors is a key factor in regulating cell proliferation and organ size via Hippo signaling pathway. Recent studies have revealed that a missense mutation in human TEAD1 is genetically linked to Sveinsson's chorioretinal atrophy (SCRA). To clarify the molecular mechanisms, we established a tetracycline-induclibe cell line which can express the mutant protein by adding tetracycline. The induction of missense mutation reduced the expression of a CTGF promoter-drived reporter gene. In fact, the mutation also abolished the transcriptional activity of the reporter gene under the co-expression of YAP or TAZ, suggesting the mutant act as a dominant-negative form on the transcriptional activity of Tead1. These results suggest that the mutant Tead1 repress the expression of Tead1 target genes and the proliferation of retinal pigment epithelial cells.