spaceprovided) Understanding the function and regulation of molecules involved in Vascular endothelial growth factor (Vegt) signaling and it's role in blood vessel development have become of increasing significance since the mechanisms that drive this process are the same as those used by vascular pathologies. A better understanding of this developmental process will be key in the development of therapies and diagnoses of many vascular disorders such as heart disease, cancer, and diabetes. The use of a pliable vertebrate genetic system such as the Zebrafish makes the study of blood vessel development both feasible and efficient. In this proposal we single out phospholipase C gamma 1 (plcgl) as the sole integrator of signals derived from Vegf receptors (Vegfr). Through a series of structure function analysis using mutated forms of plcgl SH2 domains and mutants in plcgl activation sites, we will determine the necessity of each of these components for blood vessel development, as well as identify key interactions between plcgl and Vegfrs that are needed to promote this process.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HL081927-03
Application #
7413317
Study Section
Special Emphasis Panel (ZRG1-DIG-B (29))
Program Officer
Meadows, Tawanna
Project Start
2006-04-30
Project End
2009-04-29
Budget Start
2008-04-30
Budget End
2009-04-29
Support Year
3
Fiscal Year
2008
Total Cost
$28,565
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Villefranc, Jacques A; Nicoli, Stefania; Bentley, Katie et al. (2013) A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development 140:1497-506
Covassin, L D; Siekmann, A F; Kacergis, M C et al. (2009) A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Dev Biol 329:212-26
Villefranc, Jacques A; Amigo, Julio; Lawson, Nathan D (2007) Gateway compatible vectors for analysis of gene function in the zebrafish. Dev Dyn 236:3077-87