ArticleThe Journal of biological chemistry2010
Pax6 controls the expression of critical genes involved in pancreatic {alpha} cell differentiation and function.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- CDKAL1-related single nucleotide polymorphisms are associated with insulin resistance in a cross-sectional cohort of Greek children.PloS one · 2014Trial
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- mNature metabolism · 2026Article
- Review
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- CK2 activity is crucial for proper glucagon expression.Diabetologia · 2024Article
- MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis.Blood advances · 2023Article
- Not the second fiddle: α cell development, identity, and function in health and diabetes.The Journal of endocrinology · 2023Review
- Article
- Small molecule glucagon release inhibitors with activity in human islets.Frontiers in endocrinology · 2023Article
- Sphingosine-1-phosphate as a key player of insulin secretion induced by high-density lipoprotein treatment.Physiological reports · 2021Article
- The Long Noncoding RNA Paupar Modulates PAX6 Regulatory Activities to Promote Alpha Cell Development and Function.Cell metabolism · 2019Article
- The transcription factorThe Journal of biological chemistry · 2017Article
- Abnormal CFTR Affects Glucagon Production by Islet α Cells in Cystic Fibrosis and Polycystic Ovarian Syndrome.Frontiers in physiology · 2017Article
- PAX4 promotes PDX1-induced differentiation of mesenchymal stem cells into insulin-secreting cells.American journal of translational research · 2017Article
- Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs.Scientific reports · 2016Article
- Glucose-dependent downregulation of glucagon gene expression mediated by selective interactions between ALX3 and PAX6 in mouse alpha cells.Diabetologia · 2016Article
- α-Cell Dysfunctions and Molecular Alterations in Male Insulinopenic Diabetic Mice Are Not Completely Corrected by Insulin.Endocrinology · 2016Article
- Mapping gene regulatory circuitry of Pax6 during neurogenesis.Cell discovery · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The paired box homeodomain Pax6 is crucial for endocrine cell development and function and plays an essential role in glucose homeostasis. Indeed, mutations of Pax6 are associated with diabetic phenotype. Importantly, homozygous mutant mice for Pax6 are characterized by markedly decreased β and δ cells and absent α cells. To better understand the critical role that Pax6 exerts in glucagon-producing cells, we developed a model of primary rat α cells. To study the transcriptional network of Pax6 in adult and differentiated α cells, we generated Pax6-deficient primary rat α cells and glucagon-producing cells, using either specific siRNA or cells expressing constitutively a dominant-negative form of Pax6. In primary rat α cells, we confirm that Pax6 controls the transcription of the Proglucagon and processing enzyme PC2 genes and identify three new target genes coding for MafB, cMaf, and NeuroD1/Beta2, which are all critical for Glucagon gene transcription and α cell differentiation. Furthermore, we demonstrate that Pax6 directly binds and activates the promoter region of the three genes through specific binding sites and that constitutive expression of a dominant-negative form of Pax6 in glucagon-producing cells (InR1G9) inhibits the activities of the promoters. Finally our results suggest that the critical role of Pax6 action on α cell differentiation is independent of those of Arx and Foxa2, two transcription factors that are necessary for α cell development. We conclude that Pax6 is critical for α cell function and differentiation through the transcriptional control of key genes involved in glucagon gene transcription, proglucagon processing, and α cell differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.