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