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Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk
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
Affiliation:Signal Transduction Program, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
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.
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