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Postnatal Lymphatic Partitioning from the Blood Vasculature in the Small Intestine Requires Fasting-Induced Adipose Factor
Fredrik Bäckhed, Peter A. Crawford, David O'Donnell and Jeffrey I. Gordon
Proceedings of the National Academy of Sciences of the United States of America
Vol. 104, No. 2 (Jan. 9, 2007), pp. 606-611
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25426149
Page Count: 6
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Lymphatic vessels develop from specialized venous endothelial cells. Using knockout mice, we found that fasting-induced adipose factor (Fiaf) is required for functional partitioning of postnatal intestinal lymphatic and blood vessels. In wild-type animals, levels of intestinal Fiaf expression rise during the first postnatal day and peak at day 2, which coincides with the onset of the lymphatico-venous partitioning abnormality in Fiaf-/- mutants on a mixed 129/SvJ:C57BL/6 genetic background. Fiaf deficiency is not associated with disruption of the blood vasculature or with lymphatic endothelial recruitment of smooth muscle cells. We identified Prox1, a critical regulator of lymphangiogenesis, as a downstream target for Fiaf signaling in the intestinal lymphatic endothelium. This organ-specific lymphovascular abnormality can be rescued by allowing embryonic Fiaf-/- intestinal isografts to develop in Fiaf+/+ recipients.
Proceedings of the National Academy of Sciences of the United States of America © 2007 National Academy of Sciences