Pdx1

PDX1, also known as IPF1 (insulin promoter factor 1), is a homeobox transcription factor essential for pancreas development and beta-cell function. The human PDX1 gene encodes a 283-amino-acid protein with a homeodomain that binds DNA and activates transcription of insulin and other beta-cell–related genes. PDX1 is expressed in pancreatic progenitor cells during development and remains active in mature pancreatic beta cells, with additional expression in the developing duodenum.

PDX1 plays a central role in pancreatic organogenesis. In mice, loss of Pdx1 function causes pancreatic agenesis, illustrating its necessity for pancreatic tissue formation. In humans, pathogenic PDX1 variants are linked to maturity-onset diabetes of the young type 4 (MODY4) and, in more severe cases with biallelic mutations, pancreatic agenesis or exocrine insufficiency. Haploinsufficiency or regulatory variations can contribute to diabetes susceptibility in some individuals.

Mechanistically, PDX1 binds the insulin gene promoter and directly regulates insulin transcription, while also controlling a network of beta-cell genes such as GLUT2, glucokinase, and other transcriptional factors. It functions in concert with NeuroD1, MafA, Nkx6.1, and PAX6 to maintain beta-cell identity and promote glucose-responsive gene expression. PDX1 activity is modulated by signaling pathways and post-translational modifications that influence its DNA binding and transactivation capacity.

In research and medicine, PDX1 is a key factor in differentiation and cellular reprogramming strategies aimed at generating insulin-producing cells from stem cells or fibroblasts, often used alongside other factors (e.g., Ngn3, MafA). Its study informs diabetes biology and potential regenerative therapies.