Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.
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.
Abtahian
Farhad
F
Signal Transduction Program, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Guerriero
Anastasia
A
Sebzda
Eric
E
Lu
Min-Min
MM
Zhou
Rong
R
Mocsai
Attila
A
Myers
Erin E
EE
Huang
Bin
B
Jackson
David G
DG
Ferrari
Victor A
VA
Tybulewicz
Victor
V
Lowell
Clifford A
CA
Lepore
John J
JJ
Koretzky
Gary A
GA
Kahn
Mark L
ML
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000378:metabolism; D001808:Blood Vessels / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016026:Bone Marrow Transplantation; D003911:Dextrans; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000378:metabolism; D006470:Hemorrhage; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D047908:Intracellular Signaling Peptides and Proteins; D008208:Lymphatic System / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008638:Mesenteric Arteries / Q000002:abnormalities; D008642:Mesenteric Veins / Q000002:abnormalities; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology; D000072377:Syk Kinase; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D014680:Veins / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D048868:Adaptor Proteins, Signal Transducing; D018952:Antigens, CD34; D003911:Dextrans; D004792:Enzyme Precursors; D016650:Fluorescein-5-isothiocyanate; D006023:Glycoproteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3; D000098551:Prospero-Related Homeobox 1 Protein; C092947:SLP-76 signal Transducing adaptor proteins; C492273:LYVE1 protein, mouse; C015219:fluorescein isothiocyanate dextran; C000606897:Syk protein, mouse