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Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.

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.

SUBMITTER: Abtahian F

PROVIDER: S-EPMC2982679 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.

Abtahian Farhad F 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

Science (New York, N.Y.) 20030101 5604

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 ...[more]

PMID: 12522250

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ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters.

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