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Research progress

2012-2013: Proposed research project 19

Molecular mechanism underlying the Hippo pathway-mediated three dimensional construction of the neural tube and blood vessel system
Leader : Yoichi Asaoka
Research progress

In recent years, the Hippo signaling pathway has emerged as a central regulator of growth in epithelial tissues, but the molecular mechanism underlying the three dimensional (3D) construction of the epithelial tubular structures is poorly understood. Previously, our group carried out a morphological screening in medaka embryos. We identified a mutant of YAP, the nuclear executor of the Hippo pathway that causes a flattened body in which individual epithelial tubules collapse and are not properly aligned. In this research project, we have challenged to clarify the molecular and cellular pathogenesis of epithelial organ collapse in YAP mutant and so far obtained the following findings. (1) To monitor the cytoskeletal tension in the developing medaka embryos, we adapted the fluorescent vinculin tension sensor (VinTS) system. At present, the FRET efficiency is very low and we are trying to find the optimum length and type of the linker to obtain the maximal gain of FRET (unpublished data). (2) To investigate the molecular mechanisms in which the Hippo signaling pathway affects epithelial tissue morphogenesis, we carried out the mutational analysis of YAP. We found that the TEAD-binding and WW domains of YAP all play a pivotal role in the regulation of retinogenesis (submitted).