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epsin NH2-terminal homology domain
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Prado et al (2004) have shown that absence of the homeodomain protein Nkx2.2, which is essential for the differentiation of all beta-cells and a subset of A-cells, contain relatively normal sized islets, but a large number of cells within the mutant islets that fail to produce any of the four major islet hormones. These cells are seen also in mutant mice lacking expression of Pax4.
In mutant animals islet endocrine cells are replaced by cells that produce the hormone ghrelin. These cells, termed epsilon cells, are found in low numbers also in normal mouse pancreas and constitute a cell population different from other an islet cells. Wierup et al (2002) have shown that Ghrelin is not co-expressed with any known islet hormone in these cells. The cells are being referred to also as ghrelin cells (Gr cells) and are the same as X/A-like cells or A-like cells. The term Pancreatic ghrelin cells has been proposed for Epsilon cells (Helander and FŠndriks, 2012).
The authors have proposed that insulin cells (beta-cells) and ghrelin cells share a common progenitor and that Nkx2.2 and Pax4 are required to specify or maintain differentiation of the beta-cell fate. Heller et al (2005) have demonstrated that pancreatic epsilon cells derive from precursor cells that express Neurogenin-3 and that their development depends on Neurogenin-3 activity. Lack of the homeodomain-containing transcription factor Arx leads to mutant mice lacking A-cells expressing ghrelin and glucagon. The population of ghrelin cells is not affected in mice lacking either Arx or Pax4. Loss of Pax6 provokes an unexpected increase of epsilon cell number which is not due to increased proliferation. Chao et al (2007) have shown that the A-cell, PP cell and epsilon cell phenotypes of the Nkx2.2 knock-out mice are rescued partially by the simultaneous elimination of NeuroD1.
Arnes et al (2012) have reported that the epsilon cells that produce ghrelin do not represent a terminally differentiated endocrine cell population in the mouse pancreas. These Ghrelin cells give rise to significant numbers of A-cells and PP cells and rare Beta-cells in the adult islet. These cells are maintained also in pancreata lacking the essential endocrine lineage regulator Neurogenin 3, and retain the ability to contribute to cells within the pancreatic ductal and exocrine lineages. Thus, epsilon cells represent a multipotent progenitor cell population that delineates a major subgrouping of the islet endocrine cell populations.
For related information of interest see also: Cell types.
Copyright © 2012 by H IBELGAUFTS. All rights reserved.
ENTRY LAST MODIFIED: September 2012
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