Developmental Expression of the Homeodomain Protein IDX-1 in Mice Transgenic for an IDX-1 Promoter/lacZ Transcriptional Reporter1

Abstract

Expression of the homeodomain transcription factor IDX-1 (also known as IPF-1, STF-1, and PDX-1) is required for pancreas development, because disruption of the gene in mice and humans results in pancreatic agenesis. During embryonic development the idx-1 gene is first expressed in a localized region of foregut endoderm from which the duodenum and pancreas later develop. To more fully understand the role of IDX-1 in pancreas development, transgenic mice expressing the Escherichia coli lacZ gene under control of the 5'-proximal 4.6 kb of the idx-1 promoter were created as a reporter for the developmental expression of IDX-1. Here we show that the determinants for the developmental and tissue-specific expression of the endogenous idx-1 gene are faithfully reproduced by the 4.6-kb region of the idx-1 promoter. Expression of lacZ is detected in the development of the exocrine and endocrine pancreas in pancreatic ducts, common bile and cystic ducts, pyloric glands of the distal stomach, Brunner's glands, the intestinal epithelium of the duodenum, and the spleen. The observed spatial and temporal pattern of lacZ expression directed by the IDX-1 promoter further supports an important role of IDX-1 in specifying the development of several endodermal structures within the midsegment of the body. An unexpected finding is that IDX-1 promoter-driven (transcriptional) lacZ activity does not always coincide with the localization of IDX-1 messenger RNA by in situ hybridization and IDX-1 protein by immunocytochemistry in adult rat duodenum, suggesting the existence of regulation of IDX-1 expression at the posttranscriptional level of expression of the idx-1 gene.

Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis

“…The transcription factor (TF) Pdx1 plays essential roles in pancreatic tissue development and differentiation of pancreatic cell lineages ( 14 ). In adult mice, Pdx1 is expressed only in specific cell types, such as acinar cells, β cells of the islets, and ductal cells ( 15 – 17 ). To examine the specificity of Pdx1-Cre–mediated miR-29a depletion in our murine model, we measured miR-29a levels in acinar cells, islets, and PSCs in the mouse pancreata.…”

DNA methylation in human gastric epithelial cells allows cell type-related plasticity and defines regional identity

“…2C). Interestingly, among genes most affected by differential methylation, we identified the pan-stomach developmental regulator GATA Binding Protein 4 (GATA4), Pancreatic And Duodenal Homeobox 1 (PDX1), which is a transcription factor essential for the development of the pancreas and gastroduodenal junction and expressed in gastric antrum (Holland et al, 2013;Offield et al, 1996;Stoffers et al, 1999), as well as Iroquois Homeobox 2 and 5 (IRX2 and IRX5), which have been implicated in the specification of stomach fundus in mice (McCracken et al, 2017) (Fig. 2A).…”

PDX-1: A Promising Therapeutic Target to Reverse Diabetes

“…In contrast, its expression is low in some ductal and acinar cells [ 58 , 59 ]. Stoffers et al found that PDX-1 played an important role in developing the exocrine and endocrine portions of the pancreas, pancreatic ducts, pyloric glands of the distal stomach, common bile and cystic ducts, the intestinal epithelium of the duodenum, Brunner’s glands, and the spleen [ 60 ]. In addition to the gastrointestinal system, PDX-1 is expressed in embryonic brain cells during the active nervous system generation phase [ 61 ].…”