Syk and Slp-76 Mutant Mice Reveal a Cell-Autonomous Hematopoietic Cell Contribution to Vascular Development

Eric Sebzda, Chris Hibbard, Shawn Sweeney, Farhad Abtahian, Natalie Bezman, Gina Clemens, Jonathan S. Maltzman, Lan Cheng, Feiyan Liu, Martin Turner, Victor Tybulewicz, Gary A. Koretzky, Mark L. Kahn

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish
Pages (from-to)349-361
Number of pages13
JournalDevelopmental cell
Volume11
Issue number3
DOIs
StatePublished - Sep 2006

Keywords

  • DEVBIO
  • SIGNALING
  • STEMCELL

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