ArticleBMC developmental biology2011
Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage.
Article in BMC developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Role of Nkx2.2 immunohistochemistry in distinguishing Ewing sarcoma from neuroendocrine neoplasms at different sites.Journal of Taibah University Medical Sciences · 2026Article
- Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus.Stem cell research & therapy · 2024Review
- Major β cell-specific functions of NKX2.2 are mediated via the NK2-specific domain.Genes & development · 2023Article
- mTOR Signaling in X/A-Like Cells Contributes to Lipid Homeostasis in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Gene Signature of the Human Pancreatic ε Cell.Endocrinology · 2018Article
- NKX2.2, PDX-1 and CDX-2 as potential biomarkers to differentiate well-differentiated neuroendocrine tumors.Biomarker research · 2018Article
- Loss of the imprinted, non-coding Snord116 gene cluster in the interval deleted in the Prader Willi syndrome results in murine neuronal and endocrine pancreatic developmental phenotypes.Human molecular genetics · 2017Article
- Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx.Cell metabolism · 2017Article
- Pancreatic regeneration: basic research and gene regulation.Surgery today · 2016Review
- Transcription factor regulation of pancreatic organogenesis, differentiation and maturation.Islets · 2016Review
- Generation of a Conditional Allele of the Transcription Factor Atonal Homolog 8 (Atoh8).PloS one · 2016Article
- Inactivating the permanent neonatal diabetes gene Mnx1 switches insulin-producing β-cells to a δ-like fate and reveals a facultative proliferative capacity in aged β-cells.Development (Cambridge, England) · 2015Article
- Role of transcription factors in the transdifferentiation of pancreatic islet cells.Journal of molecular endocrinology · 2015Review
- Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease.Cell stem cell · 2015Article
- Gene network-based analysis identifies two potential subtypes of small intestinal neuroendocrine tumors.BMC genomics · 2014Article
- Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function.Molecular and cellular biochemistry · 2013Article
- Gene regulatory networks governing pancreas development.Developmental cell · 2013Review
- Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas.PLoS genetics · 2013Article
- Ghrelin, the proglucagon-derived peptides and peptide YY in nutrient homeostasis.Nature reviews. Gastroenterology & hepatology · 2012Review
- Ghrelin expression in the mouse pancreas defines a unique multipotent progenitor population.PloS one · 2012Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundNkx2.2 and Arx represent key transcription factors implicated in the specification of islet cell subtypes during pancreas development. Mice deficient for Arx do not develop any alpha-cells whereas beta- and delta-cells are found in considerably higher numbers. In Nkx2.2 mutant animals, alpha- and beta-cell development is severely impaired whereas a ghrelin-expressing cell population is found augmented.Notably, Arx transcription is clearly enhanced in Nkx2.2-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of Nkx2.2/Arx single- and double-mutants but also of Pax6-deficient animals.
resultsWe show that most of the ghrelin+ cells emerging in pancreata of Nkx2.2- and Pax6-deficient mice, express the alpha-cell specifier Arx, but also additional beta-cell related genes. In Nkx2.2-deficient mice, Arx directly co-localizes with iAPP, PC1/3 and Pdx1 suggesting an Nkx2.2-dependent control of Arx in committed beta-cells. The combined loss of Nkx2.2 and Arx likewise results in the formation of a hyperplastic ghrelin+ cell population at the expense of mature alpha- and beta-cells. Surprisingly, such Nkx2.2-/-Arx- ghrelin+ cells also express the somatostatin hormone.
conclusionsOur data indicate that Nkx2.2 acts by reinforcing the transcriptional networks initiated by Pax4 and Arx in early committed beta- and alpha-cell, respectively. Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in early committed beta-cells.
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