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Gerard A. Lutty, Ines Galtier d’Auriac, D. S. McLeod; Association Of Runx1 With Vascular Development In The Fetal Human Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2536.
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© ARVO (1962-2015); The Authors (2016-present)
Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) is a transcription factor that is essential for definitive hematopoiesis and regulates the differentiation of hematopoietic stem cells into mature blood. RUNX1 is required for blood and vessel development at the hemangioblast level in Zebra fish. We have found that both the human choriocapillaris (CC) and fetal vasculature of vitreous (FVV) develop by hemo-vasculogenesis, development of blood and blood vessels from hemangioblasts (1, 2). Thus we investigated the association of RUNX1 with development of these vasculatures in fetal human eyes.
Fetal human eyes [7-21 weeks gestation(WG)] were cryopreserved and sections incubated with antibodies against RUNX1, CXCR4, cKit, and CD31. Analysis was performed on Zeiss meta 710 confocal microscope.
RUNX1 was present in the cytoplasm of progenitors forming the FVV at 7 WG. From 10-17 WG, RUNX1 was prominently localized to the nucleus of endothelial cells (ECs) and presumed pericytes in developing FVV. At 14-17 WG, RUNX1 was prominent in subnuclear compartments of both cell types. RUNX1 was present in cytoplasm of some cells in the islands of progenitors in the 7 WG developing CC, but nuclear localization was far more prominent at 10-21 WG. It appeared that pericytes and EC in CC expressed RUNX1 as well as the mesenchymal precursors throughout choroidal stroma. RUNX1 was also associated with angioblasts in inner retina as they assembled by vasculogenesis. Also RUNX1 was present in the inner neuroblastic layer progenitor pool that we have previously found to express CXCR4 and cKit. As these progenitors differentiate into ganglion cells and EC, RUNX1 expression diminished.
Conclusions: RUNX1 was associated with vascular progenitors in developing CC, FVV, and retina. Expression declined as ECs matured in the retinal vasculature but remained prominent in EC of CC and FVV that form by hemo-vasculogenesis.1. Hasegawa T, et al. Developmentof the choriocapillaris by hemovasculogenesis. Dev Dyn 2007;236:2089-100.2. Lutty G, et al, Developmentof the fetal vasculature of vitreous by hemovasculogenesis. ARVO, 2006.
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