Laura Crawford's Research
THE ROLE OF CTGF IN ISLET MORPHOGENESIS AND BETA CELL PROLIFERATION
My primary interest when I entered the lab was to better understand factors critical to make a pancreatic islet with the characteristic morphology. Using a technique known as microarray analysis, we compared the gene expression profiles of wild-type mice to that of a transgenic mouse line that exhibits abnormal islet morphology. We were particularly interested in identifying genes that may be involved in regulating cell adhesion, migration, communication, and sorting, which are processes likely to occur during islet morphogenesis. From this analysis, we identified a gene known as connective tissue growth factor (CTGF) that is expressed at a lower level in the pancreata of the transgenic mice. This secreted factor had been shown in other tissues to play a role in the process we were interested in. I subsequently found that CTGF is expressed in beta cells of the pancreas during late gestation and early postnatal life, but this expression is extinguished by one week of age and in adult mice. Thus, during pancreas development, CTGF expression correlates with a time when there is a great deal of beta cell proliferation. I also found that CTGF is re-expressed in the islets of pregnant mice, again during a time of high beta cell proliferation. Mice in which CTGF is globally deleted (CTGF-/-) die after birth, but examination of their pancreas during embryogenesis revealed islets and ducts with altered morphology. The islet phenotype closely resembles that seen in the transgenic mouse line that was originally used for the microarray studies in which we identified CTGF. Within the islets of CTGF-/- embryos, there is an increased number of glucagon producing cells, and during late embryogenesis there is a reduction in beta cell proliferation. This evidence together suggests that CTGF is an important regulator of beta cell replication and islet development.
