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PMID: 12522250 Published · ppublish English Journal Article

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

Science (New York, N.Y.) ·Vol. 299 ·No. 5604 ·2003-01-10 ·Pages 247-51

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

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Animals, Newborn Antigens, CD34/metabolism Blood Vessels/abnormalities,cytology,embryology,metabolism Bone Marrow Cells/cytology,physiology Bone Marrow Transplantation Dextrans Endothelium, Lymphatic/cytology,metabolism Endothelium, Vascular/cytology,metabolism Enzyme Precursors/genetics,metabolism Fluorescein-5-isothiocyanate/analogs & derivatives Glycoproteins/metabolism Hemorrhage Homeodomain Proteins/genetics,metabolism Intestines/blood supply Intracellular Signaling Peptides and Proteins Lymphatic System/abnormalities,cytology,embryology,metabolism Membrane Transport Proteins Mesenteric Arteries/abnormalities Mesenteric Veins/abnormalities Mice Phosphoproteins/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Signal Transduction Stem Cells/physiology Syk Kinase Tumor Suppressor Proteins Vascular Endothelial Growth Factor Receptor-3/metabolism Veins/cytology,embryology,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Antigens, CD34 Dextrans Enzyme Precursors Glycoproteins Homeodomain Proteins Intracellular Signaling Peptides and Proteins Membrane Transport Proteins Phosphoproteins SLP-76 signal Transducing adaptor proteins Tumor Suppressor Proteins Xlkd1 protein, mouse fluorescein isothiocyanate dextran prospero-related homeobox 1 protein Protein-Tyrosine Kinases Vascular Endothelial Growth Factor Receptor-3 Syk Kinase Syk protein, mouse Fluorescein-5-isothiocyanate
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Abtahian Farhad
Signal Transduction Program, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
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
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1079477
Published
2003-01-10
Pages
247-51
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2982679
Subset
IM
Grants
NIBIB NIH HHS · R21 EB002473 · United States
NIBIB NIH HHS · R21 EB002473-02 · United States
Corrections
CommentIn
PMID: 12522236
External Links
PubMed source DOI: 10.1126/science.1079477 PMC Full Text View journal details
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