Platelet derived growth factor receptors (PDGFRa and PDGFRa) are receptor tyrosine kinases that play an important role in the development and function of many mesenchymal cell types including vascular smooth muscle cells and lung alveolar smooth muscle cells. When these receptors bind ligand, they are capable of activating a multitude of signal transduction pathways within the cell, resulting in proliferation, differentiation, and migration. Although the receptors' signal transduction has been studied for many years, their roles in vivo remain elusive. The long term goals of this proposal are to understand how these signal transduction pathways translate to cellular responses and apply this knowledge to understanding the function of this family of receptors in vascular biology and mesenchymal cell development. To attain this goal, a panel of mice that afford the unique opportunity to investigate signal transduction in living tissues has been generated. These mice will be used in a series of experiments designed to address the role of biochemical signals in the heart, the kidney, and the eye.
The specific aims of this proposal are to: 1) study the function of the PDGFRa in development and signal transduction of mural cells (vascular smooth muscle cells and pericytes); and 2) identify the function of phosphoinositide-3 kinase downstream of both PDGF receptors during mammalian embryogenesis. The knowledge gained from these studies will provide essential information regarding the mechanisms of receptor mediated intracellular signal transduction within mammalian tissues. In addition, these experiments will offer necessary details regarding the function of PDGF receptors in mesenchymal cells especially those that provide support for blood vessels. This understanding could lead to novel approaches for controlling this cell population during development and in disease states.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL074257-03
Application #
6893349
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Schramm, Charlene A
Project Start
2003-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$436,800
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Green, Christopher Daniel; Ma, Qianyi; Manske, Gabriel L et al. (2018) A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq. Dev Cell 46:651-667.e10
Tallquist, Michelle D (2018) Cardiac fibroblasts: from origin to injury. Curr Opin Physiol 1:75-79
Ivey, Malina J; Kuwabara, Jill T; Pai, Jonathan T et al. (2018) Resident fibroblast expansion during cardiac growth and remodeling. J Mol Cell Cardiol 114:161-174
Kuwabara, Jill T; Tallquist, Michelle D (2017) Tracking Adventitial Fibroblast Contribution to Disease: A Review of Current Methods to Identify Resident Fibroblasts. Arterioscler Thromb Vasc Biol 37:1598-1607
Kanisicak, Onur; Khalil, Hadi; Ivey, Malina J et al. (2016) Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun 7:12260
Pinto, Alexander R; Ilinykh, Alexei; Ivey, Malina J et al. (2016) Revisiting Cardiac Cellular Composition. Circ Res 118:400-9
Swonger, Jessica M; Liu, Jocelyn S; Ivey, Malina J et al. (2016) Genetic tools for identifying and manipulating fibroblasts in the mouse. Differentiation 92:66-83
McCarthy, Neil; Liu, Jocelyn S; Richarte, Alicia M et al. (2016) Pdgfra and Pdgfrb genetically interact during craniofacial development. Dev Dyn 245:641-52
Ivey, Malina J; Tallquist, Michelle D (2016) Defining the Cardiac Fibroblast. Circ J 80:2269-2276
Nurnberg, S T; Cheng, K; Raiesdana, A et al. (2015) Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells that Contribute to the Fibrous Cap. Genom Data 5:36-37

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