Studies on an essential factor for gut growth
During a human's lifetime the intestines produce an extraordinary number of cells. This requires almost unimaginable numbers of cell divisions. The factors that control this process are largely unknown despite many years of intense investigation. We have discovered that a factor (CSF-1) long known to be important in the regulation of phagocytic or macrophage cells also has potent activity in both the small and large intestine. Using genetic evidence where mice with mutations in the gene that encodes this factor or in the gene that encodes the receptor for the factor we have been able to gather convincing evidence that this factor is an essential intestine growth factor. Three consequences of disrupting the action of this factor are reduced growth of the cells in the crypts where new cells are born, loss of intestinal structure or architecture and finally in the small intestine, the complete absence of Paneth cells. These cells are now considered to be very important in the pathogenesis or cause of disorders like inflammatory bowel disease. However, very little about what specifically drives their production is known so the discovery of CSF-1 as a factor involved in their genesis is very exciting. Finally, the type of growth signals that molecules like CSF-1 provide cells are also those which are subverted in the process of carcer. We are now in position to investigate this perspective of growth signalling by CSF-1 in intestinal cells for the first time.
Associate Professor Robert Ramsay, Associate Professor Ivan Bertoncello & Professor Evan Stanley