Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor

Fredrik Bäckhed, Peter A. Crawford, David O'Donnell, Jeffrey I. Gordon

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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 lymphaticovenous 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.

Original languageEnglish (US)
Pages (from-to)606-611
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number2
DOIs
StatePublished - Jan 9 2007

Keywords

  • Angiopoietin-like proteins
  • Postnatal gut development
  • organ-specific regulator of lymphangiogenesis

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