Pdx1 (Pancreatic and duodenal homeobox 1), also known as insulin promoter factor 1, is a transcription factor necessary for pancreatic development and β-cell maturation. Pdx1 (in rodents), otherwise known as Ipf1 (in humans), is the gene encoding it.[1]
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In embryonic development, Pdx1 is expressed by a population of cells in the posterior foregut region of the definitive endoderm, and Pdx1+ epithelial cells give rise to the developing pancreatic buds, and eventually, the whole of the pancreas—its exocrine, endocrine, and ductal cell populations.[2] Pancreatic Pdx1+ cells first arise at mouse embryonic day 8.5-9.0 (E8.5-9.0), and Pdx1 expression continues until E12.0-E12.5,[3] after which Pdx1 expression decreases and the pancreas is formed—other transcription factors are expressed, controlling the fates of the cells of the newly formed pancreas.[4] Homozygous Pdx1 knockout mice form pancreatic buds but fail to develop a pancreas,[4] and transgenic mice in which tetracycline application results in death of Pdx1+ cells are almost completely apancreatic if doxycycline (tetracycline derivative) is administered throughout the pregnancy of these transgenic mice, illustrating the necessity of Pdx1+ cells in pancreatic development.[3]
Pdx1 is also necessary for β-cell maturation: developing β-cells co-express Pdx1, Nkx6-1, and insulin, a process that results in the silencing of MafB and the expression of MafA, a necessary switch in maturation of β-cells.[2] Pdx1 appears to also play a role in the fating of endocrine cells, encoding for insulin and somatostatin, two pancreatic endocrine products, while repressing glucagon. Thus, Pdx1 expression apparently favors the production of insulin+ β-cells and somatostatin+Δ-cells rather than glucagon+ α-cells.
Pdx1+ pancreatic progenitor cells also co-express Hlxb9, Hnf6, Ptf1a and Nkx6-1, and these progenitor cells form the initial pancreatic buds, which further proliferate and branch in response to FGF-10 signaling. Afterwards, fating of the pancreatic cells begins; a population of cells has Notch signaling inhibited, and subsequently, expresses Ngn3. This Ngn3+ population is a transient population of pancreatic endocrine progenitors that gives rise to the α, β, Δ, PP, and ε cells of the Islets of Langerhans.[3] Other cells will give rise to the exocrine and ductal pancreatic cell populations.
Mutations in the Pdx1 gene may be involved in several pancreatic pathologies, possibly diabetes mellitus.[5]
Pdx1 has been shown to interact with MAFA.[6]
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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