Pdx1
Encyclopedia
Pdx1 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.
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. 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 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.
, and insulin
, a process that results in the silencing of MafB
and the expression of MafA
, a necessary switch in maturation of β-cells. 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.
, 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
. Other cells will give rise to the exocrine and ductal
pancreatic cell populations.
.
with MAFA
.
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
necessary for pancreatic
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
development and β-cell maturation. Pdx1 (in rodents), otherwise known as Ipf1 (in humans), is the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
encoding it.
Pancreatic development
In embryonic development, Pdx1 is expressed by a population of cells in the posterior foregutForegut
The foregut is the anterior part of the alimentary canal, from the mouth to the duodenum at the entrance of the bile duct. At this point it is continuous with the midgut...
region of the definitive endoderm, and Pdx1+ epithelial cells give rise to the developing pancreatic buds
Pancreatic bud
The ventral and dorsal pancreatic buds are outgrowths of the duodenum during human embryogenesis. They join together to form the adult pancreas....
, 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 tetracycline application results in death of Pdx1+ cells are almost completely apancreatic if doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
(tetracycline derivative) is administered throughout the pregnancy of these transgenic mice, illustrating the necessity of Pdx1+ cells in pancreatic development.
β-cell Maturation
Pdx1 is also necessary for β-cell maturation: developing β-cells co-express Pdx1, Nkx6-1NKX6-1
Homeobox protein Nkx-6.1 is a protein that in humans is encoded by the NKX6-1 gene.- Function :In the pancreas, NKX6.1 is required for the development of beta cells and is a potent bifunctional transcription regulator that binds to AT-rich sequences within the promoter region of target...
, and insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, a process that results in the silencing of MafB
MAFB
MAFB can refer to:* MAFB, a human gene that encodes the MafB transcription factor* March Joint Air Reserve Base * Maxwell Air Force Base in Montgomery, Alabama* Minot Air Force Base in Minot, North Dakota...
and the expression of MafA
Mafa
Mafa is a Local Government Area of Borno State, Nigeria. Its headquarters are in the town of Mafa.It has an area of 2,869 km² and a population of 103,518 at the 2006 census.The postal code of the area is 611....
, a necessary switch in maturation of β-cells. Pdx1 appears to also play a role in the fating of endocrine cells, encoding for insulin and somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
, two pancreatic endocrine products, while repressing glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
. Thus, Pdx1 expression apparently favors the production of insulin+ β-cells and somatostatin+Δ-cells rather than glucagon+ α-cells.
Transcriptional Network
Pdx1+ pancreatic progenitor cells also co-express Hlxb9MNX1
Motor neuron and pancreas homeobox 1 also known as Homeobox HB9 , is a human gene.It can be associated with Currarino syndrome....
, Hnf6, Ptf1a
PTF1A
Pancreas transcription factor 1 subunit alpha is a protein that in humans is encoded by the PTF1A gene.-Further reading:...
and Nkx6-1
NKX6-1
Homeobox protein Nkx-6.1 is a protein that in humans is encoded by the NKX6-1 gene.- Function :In the pancreas, NKX6.1 is required for the development of beta cells and is a potent bifunctional transcription regulator that binds to AT-rich sequences within the promoter region of target...
, 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
Notch
Notch may refer to:* The nock of an arrow* Notch , a Hip hop, R&B, reggae, dancehall and reggaeton artist* Notch signaling pathway, a cell signaling system present in most multicellular organisms...
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
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
. Other cells will give rise to the exocrine and ductal
Ductal
Ductal is a proprietary pre-mixed ultra-high performance concrete whose physical characteristics exceed those of common concrete used in the construction of buildings. It is manufactured by Lafarge and Bouygues. Ductal has high compressive strength and flexural resistance compared to other concretes...
pancreatic cell populations.
Pathology
Mutations in the Pdx1 gene may be involved in several pancreatic pathologies, possibly diabetes mellitusDiabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
.
Interactions
Pdx1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with MAFA
MAFA (gene)
Transcription factor MafA is a protein that in humans is encoded by the MAFA gene.-Interactions:MAFA has been shown to interact with NEUROD1 and Pdx1.-Further reading:...
.