Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor.
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.
Bäckhed
Fredrik
F
Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108, USA.
Crawford
Peter A
PA
O'Donnell
David
D
Gordon
Jeffrey I
JI
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D000818:Animals; D000831:Animals, Newborn; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000502:physiology; D007421:Intestine, Small / Q000098:blood supply* / Q000254:growth & development* / Q000637:transplantation; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology; D042601:Lymphatic Vessels / Q000033:anatomy & histology*; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000254:growth & development; D014185:Transplantation, Isogeneic; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001798:Blood Proteins; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein