PDX1

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PDX1
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_000209

NM_008814

RefSeq (protein)

NP_000200

NP_032840

Location (UCSC)Chr 13: 27.92 – 27.93 MbChr 5: 147.21 – 147.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

PDX1 (pancreatic and duodenal homeobox 1), also known as insulin promoter factor 1, is a

mammals.[9] Coelacanth and cartilaginous fish are, so far, the only vertebrates shown to have two Pdx genes, Pdx1 and Pdx2.[10]

Function

Pancreatic development

In

epithelial cells give rise to the developing pancreatic buds, and eventually, the whole of the pancreas—its exocrine, endocrine, and ductal cell populations.[11] 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.[12] Homozygous Pdx1 knockout mice form pancreatic buds but fail to develop a pancreas,[13] 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.[12]

Pdx1 is accepted as the earliest marker for pancreatic differentiation, with the fates of pancreatic cells controlled by downstream transcription factors.

ductal
pancreatic cell populations.

β-cell maturation and survival

The final stages of pancreas development involves the production of different

MafA, a necessary switch in maturation of β-cells.[11] At this stage of pancreas development, the experimental decrease in the expression of Pdx1 results in a production of a smaller number of β-cells and an associated increase in the number of α-cells.[14]

In the mature pancreas, Pdx1 expression seems to be required for the maintenance and survival of β-cells. For instance, experimentally reducing the level of Pdx1 expression at this stage makes β-cells produce higher amounts of glucagon,[15] suggesting that Pdx1 inhibits the conversion of β-cells into α-cells. Furthermore, Pdx1 appears to be important in mediating the effect of insulin on the apoptotic programmed cell death of β-cells: a small concentration of insulin protects β-cells from apoptosis, but not in cells where Pdx1 expression has been inhibited.[16][17]

Duodenum

Pdx1 is necessary for the development of the proximal duodenum and maintenance of the gastro-duodenal junction.

Cdx2, determines the correct cellular differentiation in the proximal gut.[18] In mature mice duodenum, several genes have been identified which are dependent on Pdx1 expression and include some affecting lipid and iron absorption.[19]

Pathology

Experiments in animal models have shown that a reduction in Pdx1 expression can cause symptoms that are characteristic of

Diabetes mellitus type 2 symptoms, has a highly divergent Pdx1 gene sequence compared with other mammals.[24]

Interactions

Pdx1 has been shown to

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000139515 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029644 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Brooke, N. M., Garcia-Fernàndez, J., & Holland, P. W. (1998). The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature, 392(6679), 920.
  6. ^ "PDX1". HGNC. Retrieved 22 April 2016.
  7. PMID 7590740
    .
  8. ^ Wright, C. V., Schnegelsberg, P., & De Robertis, E. M. (1989). XlHbox 8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. Development, 105(4), 787-794.
  9. ^ "OrthoMaM phylogenetic marker: PDX1 coding sequence". OrthoMam v10. 2019. Retrieved 24 February 2019.
  10. PMID 20463047
    .
  11. ^ .
  12. ^ .
  13. ^
  14. ^ Gannon M, Ables ET, Crawford L, et al. pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol. 2007;314(2):406-17. doi:10.1016/j.ydbio.2007.10.038
  15. ^ Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev. 1998;12(12):1763-8.
  16. PMID 12697734
    .
  17. .
  18. ^ .
  19. .
  20. ^ Fujimoto, Kei, and Kenneth S. Polonsky. "Pdx1 and other factors that regulate pancreatic β‐cell survival." Diabetes, Obesity and Metabolism 11 (2009): 30-37.
  21. PMID 18477649
    .
  22. ^ "Entrez Gene: PDX1 pancreatic and duodenal homeobox 1".
  23. PMID 11575290
    .
  24. .
  25. .

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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