[DEBUG-WINDOW 처리영역 보기]
즐겨찾기  |  뉴스레터  |  오늘의 정보 회원가입   로그인
BRIC홈 한국을 빛내는 사람들
스폰서배너광고 안내  배너1 배너2 배너3 배너4
전체보기 추천논문 상위피인용논문 인터뷰 그이후 한빛사통계
조현수 (Hyunsoo Cho) 저자 이메일 보기
조회 578  인쇄하기 주소복사 트위터 공유 페이스북 공유 
YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis
열기 Authors and Affiliations


Rationale: The Hippo pathway governs cellular differentiation, morphogenesis, and homeostasis but how it regulates these processes in lymphatic vessels is unknown.

Objective: We 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.

Methods and Results: 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.

Conclusions: We find that YAP/TAZ play promoting roles in remodelling lymphatic plexus patterning and postnatal lymphatic valve maintenance by negatively regulating Prox1 expression. We 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.

- 형식: Research article
- 게재일: 2018년 11월 (BRIC 등록일 2018-11-29)
- 연구진: 국내(교신)+국외 연구진태극기
- 분야: Developmental_Biology, Cell_Biology, Molecular_Biology
  댓글 0
조현수 님 전체논문보기 >
고규영 (KAIST, 기초과학연구원)
관련분야 논문보기



Google (by Hyunsoo Cho)
Pubmed (by Hyunsoo Cho)
프리미엄 Bio일정 Bio일정 프리미엄 안내
바이오 QC 실무과정 6기 모집
바이오 QC 실무과정 6기 모집
사전접수: ~2019.01.07
날짜: 2019.03.04~12.09
장소: 성남시 분당구 황새울로 329번길 5
임상시험종사자 생체시료분석법 이해, 생물학적동등성시험의 이해
임상시험종사자 생체시료분석법 이해, 생물학적동등성시험의 이해
사전접수: ~2018.12.20
날짜: 2018.12.20~21
장소: 한국제약바이오협회 강의장 / 이매스교육센터
한빛사 홈  |  한빛사FAQ  |  한빛사 문의 및 제안
 |  BRIC소개  |  이용안내  |  이용약관  |  개인정보처리방침  |  이메일무단수집거부
Copyright © BRIC. All rights reserved.  |  문의 member@ibric.org
트위터 트위터    페이스북 페이스북    RSS서비스 RSS