PUBLICATION

Syk and Zap-70 function redundantly to promote angioblast migration

Authors
Christie, T.L., Carter, A., Rollins, E.L., and Childs, S.J.
ID
ZDB-PUB-100126-14
Date
2010
Source
Developmental Biology   340(1): 22-29 (Journal)
Registered Authors
Childs, Sarah J., Christie, Tara, Rollins, Evvi-Lynn
Keywords
Syk, Zap-70, Vegf, intersegmental vessel, thoracic duct, migration, angioblast, zebrafish
MeSH Terms
  • Animals
  • B-Lymphocytes/metabolism
  • Blood Vessels/cytology*
  • Body Patterning/physiology
  • Cell Movement/physiology*
  • Embryo, Nonmammalian/metabolism
  • Flow Cytometry
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Phylogeny
  • Protein-Tyrosine Kinases/genetics
  • Protein-Tyrosine Kinases/metabolism*
  • Stem Cells/physiology*
  • T-Lymphocytes/metabolism
  • Thoracic Duct/cytology*
  • ZAP-70 Protein-Tyrosine Kinase/genetics
  • ZAP-70 Protein-Tyrosine Kinase/metabolism*
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
20096681 Full text @ Dev. Biol.
Abstract
Spleen tyrosine kinase (Syk) plays critical roles in B-cell and T-cell development, the maintenance of vascular integrity, and proper partitioning of the blood vascular and lymphatic vascular system. Here, we utilize the zebrafish as an in vivo system to demonstrate novel roles for Syk and the related kinase Zeta associated protein (Zap-70) in promoting angioblast migration. Partial knockdown of either gene results in early angiogenic delay of the intersegmental vessels, dorsal intersegmental vessel patterning defects, and partial loss of the thoracic duct. Higher dose knockdown of both genes results in little to no angiogenic sprouting of the intersegmental vessels, a phenotype which resembles knockdown of vegfa. Di-phosphorylated ERK, an effector of the vegfa pathway, is also down-regulated in the aorta of syk:zap double morphants. Over-expression of syk under the control of a blood-specific or vascular-specific promoter rescues sprouting defects after loss of vegfa. Together these results suggest that syk and zap-70 function redundantly in an early progenitor to promote the migration of intersegmental vessel angioblasts and lymphangioblasts that contribute to the thoracic duct, either downstream of, or in parallel to vegfa.
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