Syk and Zap-70 function redundantly to promote angioblast migration.
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 downregulated 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.
Christie
Tara L
TL
Department of Biochemistry and Molecular Biology, and Smooth Muscle Research Group, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
Carter
Alyson
A
Rollins
Evvi-Lynn
EL
Childs
Sarah J
SJ
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology*; D019521:Body Patterning / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005434:Flow Cytometry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000378:metabolism; D013897:Thoracic Duct / Q000166:cytology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D029961:Zebrafish Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase