Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development.
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.
Sebzda
Eric
E
Department of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Hibbard
Chris
C
Sweeney
Shawn
S
Abtahian
Farhad
F
Bezman
Natalie
N
Clemens
Gina
G
Maltzman
Jonathan S
JS
Cheng
Lan
L
Liu
Feiyan
F
Turner
Martin
M
Tybulewicz
Victor
V
Koretzky
Gary A
GA
Kahn
Mark L
ML
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
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