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Regulation of Blood and Lymphatic Vascular Separation by Signaling Proteins SLP-76 and Syk

Science  10 Jan 2003:
Vol. 299, Issue 5604, pp. 247-251
DOI: 10.1126/science.1079477

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: koretzky{at}mail.med.upenn.edu or markkahn{at}mail.med.upenn.edu

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