MOLECULAR MARKERS OF PANCREATIC DUCT CELL DEVELOPMENT

It has been difficult to conclusively identify (much less isolate) ductal
cell precursors in the normal pancreas. Consequently, there is a paucity
of immunological or biochemical markers available that distinguish
different ductal cell types of their precursors in the developing fetal and
adult pancreas. The studies proposed herein may identify molecular markers
of differentiation for these cells. The general goal of the project
described in this application is to use contemporary techniques of primary
cell culture, molecular biology and biochemistry to identify and
characterize gene products that are involved in the development of
differentiated pancreatic ductal cell function in humans. to accomplish
this we will: 1) Generate cDNA libraries from freshly isolated adult human
ducts or primary cultures, generate subtracted cDNA libraries between these
and fetal pancreatic cells of different developmental ages, and then
identify differentially expressed cDNAs using subtracted cDNA probes or a
differential probe hybridization strategy; and 2) Characterize the adult
and fetal ductal cells for expression of known and important products, and
also for the new cDNAs derived in the studies described above (using
antibodies and cDNA probes). It is possible that some genes involved in
developmental events in the fetal pancreas will also be identified.