expression of MafA, a necessary switch in maturation of β-cells. At this stage of pancreas development, the experimental decrease in the expression of Pdx1 results in a production of a smaller number of β-cells and an associated increase in the number of α-cells. In the mature pancreas, Pdx1 expression seems to be required for the maintenance and survival of β-cells. For instance, experimentally reducing the level of Pdx1 expression at this stage makes β-cells produce higher amounts of glucagon, suggesting that Pdx1 inhibits the conversion of β-cells into α-cells. Furthermore, Pdx1 appears to be important in mediating the effect of insulin on the apoptotic programmed cell death of β-cells: a small concentration of insulin protects β-cells from apoptosis, but not in cells where Pdx1 expression has been inhibited. Duodenum Pdx1 is necessary for the development of the proximal duodenum and maintenance of the gastro-duodenal junction. Duodenal enterocytes, Brunner's glands and entero-endocrine cells (including those in the gastric antrum) are dependent on Pdx1 expression. It is a ParaHox gene, which together with Sox2 and Cdx2, determines the correct cellular differentiation in the proximal gut. In mature mice duodenum, several genes have been identified which are dependent on Pdx1 expression and include some affecting lipid and iron absorption. Pathology Experiments in animal models have shown that a reduction in Pdx1 expression can cause symptoms that are characteristic of Diabetes mellitus type 1 and Diabetes mellitus type 2. Furthermore, expression of Pdx1 is lost in gastric cancers, suggesting a role for the gene as a tumor suppressor. Maturity onset diabetes of the young (Type 4) can be caused by heterozygous mutations in Pdx1. The fat sand rat Psammomys obesus, a species with susceptibility to Diabetes mellitus type 2 symptoms, has a highly divergent Pdx1 gene sequence compared with other mammals. Interactions Pdx1 has been shown to interact with MAFA. References Further reading External links GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus Transcription factors