DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Koh, Gou Young | - |
dc.contributor.advisor | 고규영 | - |
dc.contributor.author | Cho, Hyunsoo | - |
dc.date.accessioned | 2019-08-25T02:42:58Z | - |
dc.date.available | 2019-08-25T02:42:58Z | - |
dc.date.issued | 2019 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=842193&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/265076 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2019.2,[vi, 100 p. :] | - |
dc.description.abstract | The Hippo pathway governs cellular differentiation, morphogenesis, and homeostasis but how it regulates these processes in lymphatic vessels is unknown. Therefore, I aimed to reveal the role of the final effectors of the Hippo pathway, YAP and TAZ (YAP/TAZ), in lymphatic endothelial cell (LEC) differentiation, morphogenesis, and homeostasis in vivo and in vitro. During mouse embryonic development, LEC-specific depletion of Yap/Taz disturbed both plexus patterning and valve initiation with upregulated Prox1. Conversely, LEC-specific YAP/TAZ hyperactivation impaired lymphatic specification and restricted lymphatic sprouting with profoundly downregulated Prox1. Notably, lymphatic YAP/TAZ depletion or hyperactivation aggravated or attenuated pathologic lymphangiogenesis in mouse cornea. Mechanistically, VEGF-C activated canonical Hippo signaling pathway in LECs. Indeed, repression of PROX1 transcription by YAP/TAZ hyperactivation was mediated by recruitment of nucleosome remodeling and histone deacetylase (NuRD) complex and endogenous binding activity of TEAD to the PROX1 promoter. Furthermore, YAP/TAZ hyperactivation enhanced MYC signaling and inhibited CDKN1C, leading to cell cycle dysregulation and aberrant proliferation. I find that YAP/TAZ play promoting roles in remodelling lymphatic plexus patterning and postnatal lymphatic valve maintenance by negatively regulating Prox1 expression. I further show that YAP/TAZ act as plastic regulators of lymphatic identity and define the Hippo signaling-mediated PROX1 transcriptional programming as a novel dynamic checkpoint underlying lymphatic endothelial cell plasticity and pathophysiology. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Lymphangiogenesis▼aHippo signaling▼alymphatic endothelial cell▼aprox1 transcription factor▼aYAP/TAZ | - |
dc.subject | 림프관생성▼a히포신호전달체계▼aProx1 전사 인자▼a림프관발생▼a병적림프관신생 | - |
dc.title | Role of hippo pathway in developmental and pathologic lymphangiogenesis | - |
dc.title.alternative | 림프관 발달과 병적 림프관 생성에서 Hippo 신호전달체계의 역할 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
dc.contributor.alternativeauthor | 조현수 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.