イベント&セミナー

[発生研セミナー] 12/2(月)11:30~Max Planck研究所 渡部秀一先生

2019.11.28 ●セミナー

第372回 発生研セミナー

 

 

【日時】 12月2日(月) 11:30~12:00
【会場】 発生医学研究所 1階カンファレンス室

 

【演題】 Vgll2/3 dependent function of Teads (Tead1-4) is indispensable for maintenance of muscle stem quiescence and muscle fiber type specification through mTOR signal regulation

 

【講師】 渡部 秀一  Unit Leader
 Max-Planck Institute for Heart and Lung Research, Department I Cardiac Development and Remodelling

 

 

【要旨】
Core components of Hippo signaling pathway, YAP/WWTR1 and TEADs (Tead1-4) plays a key role controlling tissue size through the regulation of proliferation and apoptosis in multiple tissue and cell types. However, YAP/WWTR1 does not associates entire TEADs function, rather distinct cofactor, VGLLs (VGLL1-4) is known to be responsible for controlling TEADs function in tissue/cell specific manner. By the combination of RNA expression profiling as well as genome-wide TEAD1/YAP DNA binding profiling (RNA-seq and Chip-seq), here we reported specific cofactor dependent TEADs transcriptional regulation is discriminative and generates distinct outcome. Especially, a crosstalk with mTOR signaling pathway was regulated by TEADs-VGLLs specific pathway in both muscle stem cell as well as matured muscle fiber through the transcriptional regulation of known mTOR inhibitor, Deptor by YAP/WWTR1 independent manner. Physiological function of those cofactor specific regulations are also discriminative and important for muscle cell development as well as homeostasis. Muscle specific TEADs-VGLLs axis is particularly important for muscle fiber type specification as well as maintenance of satellite cell quiescence whereas the YAP/WWTR1-TEADs axis is essential for muscle stem cell self-renewal by controlling proliferative genes. Either VGLLs or TEADs depletion resulted in Deptor depression and subsequent sustain activation of mTOR. Finally, muscle fiber specification defects found in VGLLs mutant rescued by mTOR signal inhibitor Rapamycin indicating that muscle fiber type speciation regulated by TEADs-VGLLs is mediated through mTOR. These results proves a model for molecular mechanism how transcription factor modulates their activity through the association with their specific cofactor.

 

【連絡先】筋発生再生分野 小野 悠介(内線番号)6601

 

本セミナーは日本語で行われます。This seminar will be held in Japanese.

 

主催;熊本大学国際先端研究拠点
共催;トランスオミクス医学研究拠点ネットワーク形成事業