@article{ec0d205e2c634cea9871370f7a28ec8c,
title = "GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through MIR-126",
abstract = "Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves and lymphovenous valves, and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of the cell junction molecules VE-cadherin and claudin 5 in lymphatic vessels. We identified miR-126 as a target of GATA2, and miR-126−/− embryos recapitulate the phenotypes of mice lacking GATA2. Primary human lymphatic endothelial cells (HLECs) lacking GATA2 (HLECΔGATA2) have altered expression of claudin 5 and VE-cadherin, and blocking miR-126 activity in HLECs phenocopies these changes in expression. Importantly, overexpression of miR-126 in HLECΔGATA2 significantly rescues the cell junction defects. Thus, our work defines a new mechanism of GATA2 activity and uncovers miR-126 as a novel regulator of mammalian lymphatic vascular development.",
keywords = "Claudin 5, GATA2, Lymphatic vasculature, Lymphovenous valves, MIR-126, VE-cadherin",
author = "{Riaj Mahamud}, Md and Xin Geng and Ho, {Yen Chun} and Boksik Cha and Yuenhee Kim and Jing Ma and Lijuan Chen and Greggory Myers and Sally Camper and Debbie Mustacich and Marlys Witte and Dongwon Choi and Hong, {Young Kwon} and Hong Chen and Gaurav Varshney and Engel, {James Douglas} and Shusheng Wang and Kim, {Tae Hoon} and Lim, {Kim Chew} and {Sathish Srinivasan}, R.",
note = "Funding Information: This work is supported by the National Heart, Lung, and Blood Institute (R01HL131652 to R.S.S. and T.-H.K.; R01HL133216 to R.S.S. and H.C.), the National Institute of General Medical Sciences COBRE (P20 GM103441 to X.G.; PI: Dr McEver), the Oklahoma Center for Adult Stem Cell Research (4340 to R.S.S.) and the American Heart Association (16PRE31190025 to M.R.M. and 19POST34380819 to Y.-C.H.). Deposited in PMC for immediate release. Funding Information: 1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. 2Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA. 3Department of Biological Sciences and Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA. 4Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA. 5Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. 6Department of Surgery, University of Arizona, Tuscon, AZ 85724, USA. 7Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. 8Vascular Biology Program, Boston Children{\textquoteright}s Hospital, Boston, MA 02115, USA. 9Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. *These authors contributed equally to this work Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd.",
year = "2019",
doi = "10.1242/dev.184218",
language = "English (US)",
volume = "146",
journal = "Journal of Embryology and Experimental Morphology",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "21",
}