Regulation of Blood and Lymphatic Vascular Separation by Signaling Proteins SLP-76 and Syk

• Published in: Science (American Association for the Advancement of Science) 2003-01, Vol.299 (5604), p.247-251
• Main Authors: Abtahian, Farhad, Guerriero, Anastasia, Sebzda, Eric, Lu, Min-Min, Zhou, Rong, Mocsai, Attila, Myers, Erin E., Huang, Bin, Jackson, David G., Ferrari, Victor A., Tybulewicz, Victor, Lowell, Clifford A., Lepore, John J., Koretzky, Gary A., Kahn, Mark L.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Animals; Animals, Newborn; Antigens, CD34 - metabolism; Biological and medical sciences; Blood; Blood circulation disorders; Blood vessels; Blood Vessels - abnormalities; Blood Vessels - cytology; Blood Vessels - embryology; Blood Vessels - metabolism; Body Composition; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Bone Marrow Transplantation; Cellular biology; Circulatory system; Dextrans; Embryology: invertebrates and vertebrates. Teratology; Embryos; Endothelial cells; Endothelium, Lymphatic - cytology; Endothelium, Lymphatic - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Enzyme Precursors - genetics; Enzyme Precursors - metabolism; Fluorescein-5-isothiocyanate - analogs & derivatives; Fractions; Fundamental and applied biological sciences. Psychology; Glycoproteins - metabolism; Hemorrhage; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Intestines; Intestines - blood supply; Intracellular Signaling Peptides and Proteins; Lymphatic system; Lymphatic System - abnormalities; Lymphatic System - cytology; Lymphatic System - embryology; Lymphatic System - metabolism; Lymphatic vessels; Mesenteric Arteries - abnormalities; Mesenteric Veins - abnormalities; Mice; Neonates; Organogenesis. Fetal development; Organogenesis. Physiological fonctions; Phenotypes; Phosphoproteins - genetics; Phosphoproteins - metabolism; Pregnancy; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; Rodents; Signal Transduction; Stem Cells - physiology; Syk Kinase; Tumor Suppressor Proteins; Vascular diseases; Vascular Endothelial Growth Factor Receptor-3 - metabolism; Veins; Veins - cytology; Veins - embryology; Veins - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1079477

Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected in endothelial cells, and blood-filled lymphatics also arose in wild-type mice reconstituted with SLP-76-deficient bone marrow. These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals.