Age-related upregulation of Drosophila caudal gene via NF-kappaB in the adult posterior midgut.

The Drosophila midgut has emerged as a powerful model system for the investigation of fundamental cellular pathways relevant to intestinal stem cell biology. Understanding the age-related changes in the adult Drosophila midgut may provide insights into the molecular mechanisms that link aging to the modulation of adult stem cell population. The caudal-related homeobox genes encode intestine-specific transcription factors required for normal intestinal development and maintenance. Here, we demonstrate that caudal gene expression is upregulated in the adult posterior midgut in response to age and oxidative stress, and that overexpression of Caudal can stimulate cell proliferation in the adult posterior midgut. We further demonstrate that the age- and oxidative-stress-related upregulation of the caudal gene is mediated by the NF-kappaB binding site located in the 5'-flanking region of the caudal gene. Our results may contribute to an understanding of the mechanisms of age-related changes in the number and activity of intestinal stem cells and progenitors in the Drosophila adult midgut.