Michelle Guney's Research

THE ROLE OF CTGF IN PANCREATIC ISLET MORPHOLOGY

CTGF is involved in a variety of cellular processes that are also thought to be critical in islet development such as proliferation, cell adhesion, extracellular matrix degradation, and cell migration.  Using global knockout mice, our lab showed that CTGF is necessary for normal islet morphology.  Animals lacking CTGF have increased glucagon+ cells, decreased b cell proliferation, and an immature ductal network.  We found that CTGF is expressed in b cells, ducts, and blood vessels during pancreas development, but is restricted to ducts and blood vessels in adult pancreata.  Our current model is that CTGF acts to promote b cell proliferation and normal islet morphogenesis during embryogenesis.  However, it is still unknown whether the phenotype seen in mutant animals is due to loss of CTGF from ducts, endocrine cells, or a combination of both.  My project is to inactivate CTGF in the different cell types in which it is expressed in the pancreas using tissue-specific Cre lines, to determine where CTGF is required in the pancreas.  In addition, I am using an inducible CTGF transgene to over-express CTGF in the developing pancreas to test whether increased CTGF promotes endocrine differentiation. These studies will further define the mechanism by which CTGF contributes to endocrine cell replication and islet morphogenesis.