title: Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development.
abstract: Developmental studies support a common origin for blood and endothelial cells, while studies of adult angiogenic responses suggest that the hematopoietic system can be a source of endothelial cells later in life. Whether hematopoietic tissue is a source of endothelial cells during normal vascular development is unknown. Mouse embryos lacking the signaling proteins Syk and Slp-76 develop abnormal blood-lymphatic endothelial connections. Here we demonstrate that expression of GFPSlp-76 in a subset of hematopoietic cells rescues this phenotype, and that deficient cells confer focal vascular phenotypes in chimeric embryos consistent with a cell-autonomous mechanism. Endogenous Syk and Slp-76, as well as transgenic GFPSlp-76, are expressed in circulating cells previously proposed to be endothelial precursors, supporting a causal role for these cells. These studies provide genetic evidence for hematopoietic contribution to vascular development and suggest that hematopoietic tissue can provide a source of vascular endothelial progenitor cells throughout life.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Sebzda
authors.forename: Chris
authors.initials: C
authors.lastname: Hibbard
authors.forename: Shawn
authors.initials: S
authors.lastname: Sweeney
authors.forename: Farhad
authors.initials: F
authors.lastname: Abtahian
authors.forename: Natalie
authors.initials: N
authors.lastname: Bezman
authors.forename: Gina
authors.initials: G
authors.lastname: Clemens
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Maltzman
authors.forename: Lan
authors.initials: L
authors.lastname: Cheng
authors.forename: Feiyan
authors.initials: F
authors.lastname: Liu
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.forename: Victor
authors.initials: V
authors.lastname: Tybulewicz
authors.forename: Gary A
authors.initials: GA
authors.lastname: Koretzky
authors.forename: Mark L
authors.initials: ML
authors.lastname: Kahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism; D001808:Blood Vessels; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000235:genetics; D006413:Hematopoietic System / Q000196:embryology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D000072377:Syk Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D050982:GATA1 Transcription Factor; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse