A Role for All-Trans-Retinoic Acid in the Early Steps of Lymphatic Vasculature Development

Marino, Daniela; Dabouras, Vasilios; Braendli, Andre W. and Detmar, Michael (2011): A Role for All-Trans-Retinoic Acid in the Early Steps of Lymphatic Vasculature Development. In: Journal of Vascular Research, No. 3: pp. 236-251

Abstract

The molecular mechanisms that regulate the earliest steps of lymphatic vascular system development are unknown. To identify regulators of lymphatic competence and commitment, we used an in vitro vascular assay with mouse embryonic stem cell-derived embryoid bodies (EBs). We found that incubation with retinoic acid (RA) and, more potently, with RA in combination with cAMP, induced the expression of the lymphatic competence marker LYVE-1 in the vascular structures of the EBs. This effect was dependent on RA receptor (RAR)-alpha and protein kinase A signaling. RA-cAMP incubation also promoted the development of CD31+/LYVE-1+/Prox1+ cell clusters. In situ studies revealed that RAR-alpha is expressed by endothelial cells of the cardinal vein in ED 9.5-11.5 mouse embryos. Timed exposure of mouse and Xenopus embryos to excess of RA upregulated LYVE-1 and VEGFR-3 on embryonic veins and increased formation of Prox1-positive lymphatic progenitors. These findings indicate that RA signaling mediates the earliest steps of lymphatic vasculature development. Copyright (C) 2010 S. Karger AG, Basel

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1018-1172
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English