Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.
Abtahian F., Guerriero A., Sebzda E., Lu MM., Zhou R., Mocsai A., Myers EE., Huang B., Jackson DG., Ferrari VA., Tybulewicz V., Lowell CA., Lepore JJ., Koretzky GA., Kahn ML.
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.