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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.

Original publication




Journal article



Publication Date





247 - 251


Adaptor Proteins, Signal Transducing, Animals, Animals, Newborn, Antigens, CD34, Blood Vessels, Bone Marrow Cells, Bone Marrow Transplantation, Dextrans, Endothelium, Lymphatic, Endothelium, Vascular, Enzyme Precursors, Fluorescein-5-isothiocyanate, Glycoproteins, Hemorrhage, Homeodomain Proteins, Intestines, Intracellular Signaling Peptides and Proteins, Lymphatic System, Membrane Transport Proteins, Mesenteric Arteries, Mesenteric Veins, Mice, Phosphoproteins, Protein-Tyrosine Kinases, Signal Transduction, Stem Cells, Syk Kinase, Tumor Suppressor Proteins, Vascular Endothelial Growth Factor Receptor-3, Veins