PDX1

Pdx1 (Pancreatic and duodenal homeobox 1), also known as insulin promoter factor 1, is a is_associated_with::transcription factor necessary for pancreatic development and is_associated_with::β-cell maturation. Pdx1 (in rodents), otherwise known as Ipf1 (in humans), is the is_associated_with::gene encoding it.

Pancreatic development
In is_associated_with::embryonic development, Pdx1 is expressed by a population of cells in the posterior is_associated_with::foregut region of the is_associated_with::definitive endoderm, and Pdx1+ is_associated_with::epithelial cells give rise to the developing is_associated_with::pancreatic buds, and eventually, the whole of the pancreas—its exocrine, endocrine, and ductal cell populations. 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, 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. Homozygous Pdx1 knockout mice form pancreatic buds but fail to develop a pancreas, and transgenic mice in which is_associated_with::tetracycline application results in death of Pdx1+ cells are almost completely apancreatic if is_associated_with::doxycycline (tetracycline derivative) is administered throughout the pregnancy of these transgenic mice, illustrating the necessity of Pdx1+ cells in pancreatic development.

β-cell maturation and survival
Pdx1 is also necessary for is_associated_with::β-cell maturation: developing β-cells co-express Pdx1, is_associated_with::NKX6-1, and is_associated_with::insulin, a process that results in the silencing of is_associated_with::MafB and the expression of is_associated_with::MafA, a necessary switch in maturation of β-cells. Pdx1 appears to also play a role in the fating of is_associated_with::endocrine cells, encoding for insulin and is_associated_with::somatostatin, two pancreatic endocrine products, while repressing is_associated_with::glucagon. Thus, Pdx1 expression apparently favors the production of insulin+ β-cells and somatostatin+Δ-cells rather than glucagon+ α-cells. In addition to roles in beta-cell differentiation, Pdx1 is required for β-cell survival. Cells with reduced Pdx1 have an increased rate of apoptotic programmed cell death.

Transcriptional Network
Pdx1+ pancreatic progenitor cells also co-express Hlxb9, Hnf6, Ptf1a and is_associated_with::NKX6-1, and these progenitor cells form the initial pancreatic buds, which further proliferate and branch in response to is_associated_with::FGF-10 signaling. Afterwards, fating of the pancreatic cells begins; a population of cells has Notch signaling inhibited, and subsequently, expresses is_associated_with::Ngn3. This is_associated_with::Ngn3+ population is a transient population of pancreatic endocrine progenitors that gives rise to the α, β, Δ, PP, and ε cells of the is_associated_with::Islets of Langerhans. Other cells will give rise to the is_associated_with::exocrine and is_associated_with::ductal pancreatic cell populations.

Pathology
Mutations in the Pdx1 gene may be involved in several pancreatic pathologies, including is_associated_with::diabetes mellitus. Maturity onset diabetes of the young (Type 4) can be caused by heterozygous mutations in Pdx1

Interactions
Pdx1 has been shown to interact with MAFA.