Data from: GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126

Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is
necessary for the development of lymphatic valves (LVs) and lymphovenous
valves (LVVs), 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 cell junction
molecules VE-Cadherin and Claudin5 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 (GATA2ΔHLEC) have altered expression of
Claudin5 and VE-Cadherin, and blocking miR-126 activity in HLECs
phenocopies these changes in expression. Importantly, overexpression of
miR-126 in GATA2ΔHLEC significantly rescues the cell junction defects.
Thus, our work defines a new mechanism of GATA2 and uncovers miR-126 as a
novel regulator of mammalian lymphatic vascular development.