Abstract
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.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Animals, Newborn
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Antigens, CD34 / metabolism
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Blood Vessels / abnormalities
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Blood Vessels / cytology
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Blood Vessels / embryology*
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Blood Vessels / metabolism
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Bone Marrow Cells / cytology
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Bone Marrow Cells / physiology
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Bone Marrow Transplantation
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Dextrans
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Endothelium, Lymphatic / cytology
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Endothelium, Lymphatic / metabolism
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism
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Enzyme Precursors / genetics
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Enzyme Precursors / metabolism*
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Fluorescein-5-isothiocyanate / analogs & derivatives*
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Glycoproteins / metabolism
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Hemorrhage
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Intestines / blood supply
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Intracellular Signaling Peptides and Proteins
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Lymphatic System / abnormalities
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Lymphatic System / cytology
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Lymphatic System / embryology*
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Lymphatic System / metabolism
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Membrane Transport Proteins
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Mesenteric Arteries / abnormalities
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Mesenteric Veins / abnormalities
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Mice
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Signal Transduction*
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Stem Cells / physiology
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Syk Kinase
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Tumor Suppressor Proteins
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Vascular Endothelial Growth Factor Receptor-3 / metabolism
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Veins / cytology
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Veins / embryology
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Veins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD34
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Dextrans
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Enzyme Precursors
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Glycoproteins
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Transport Proteins
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Phosphoproteins
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SLP-76 signal Transducing adaptor proteins
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Tumor Suppressor Proteins
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Xlkd1 protein, mouse
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fluorescein isothiocyanate dextran
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prospero-related homeobox 1 protein
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Protein-Tyrosine Kinases
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Vascular Endothelial Growth Factor Receptor-3
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Syk Kinase
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Syk protein, mouse
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Fluorescein-5-isothiocyanate