ArticleBMC developmental biology2010
Relative roles of the different Pax6 domains for pancreatic alpha cell development.
Article in BMC developmental biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A common variant upstream of the PAX6 gene influences islet function in man.Diabetologia · 2012Pooled it
- Review
- The role of noncoding RNAs in pancreatic birth defects.Birth defects research · 2023Review
- PAX6 mutation alters circadian rhythm and β cell function in mice without affecting glucose tolerance.Communications biology · 2020Article
- Mouse models for microphthalmia, anophthalmia and cataracts.Human genetics · 2019Review
- Protecting Pax6 3' UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an Aniridia Mouse Model.Molecular therapy. Nucleic acids · 2018Article
- The Pax gene family: Highlights from cephalopods.PloS one · 2017Article
- Pax6 in Collembola: Adaptive Evolution of Eye Regression.Scientific reports · 2016Article
- Case of aniridia with a heterozygous PAX6 mutation in which the glucagon response to arginine was evaluated.Journal of diabetes investigation · 2015Article
- Pleiotropic functions for transcription factor zscan10.PloS one · 2014Article
- Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle-derived induced pluripotent stem cells of schizophrenia patients.Molecular psychiatry · 2013Article
- Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation.Development (Cambridge, England) · 2013Article
- Novel small-eye allele in paired box gene 6 (Pax6) is caused by a point mutation in intron 7 and creates a new exon.Molecular vision · 2013Article
- Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences.PLoS genetics · 2013Article
- Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain.PloS one · 2013Article
- The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas.PloS one · 2013Article
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9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe transcription factor Pax6 functions in the specification and maintenance of the differentiated cell lineages in the endocrine pancreas. It has two DNA binding domains, the paired domain and the homeodomain, in addition to a C-terminal transactivation domain. The phenotype of Pax6-/- knockout mice suggests non-redundant functions of the transcription factor in the development of glucagon-expressing alpha-cells as this cell type is absent in the mutants. We ask the question of how the differentiation of pancreatic endocrine cells, in particular that of alpha-cells, is affected by selective inactivation of either one of the three major domains of Pax6.
resultsThe Pax6Aey18 mutant mouse line, in which the paired domain is inactivated, showed a phenotype similar to that of Pax6-/- knockout mice with a near complete absence of glucagon-positive alpha-cells (0-4 cells/section; < or =1% of wt), reduced beta-cell area (74% of wt) and disorganized islets. The proportion of ghrelin-positive epsilon-cells was expanded. In Pax6Sey-Neu mutants, which lack the transactivation domain, alpha-and beta-cells where reduced to 25 and 40% of wt, respectively. We also studied two mouse lines with mutations in the homeodomain, Pax64Neu and Pax6132-14Neu. Neighboring amino acids are affected in the two lines and both point mutations abolish DNA binding of the classical P3 homeodomain target sequence. The pancreatic phenotype of the two mutants however was divergent. While Pax64Neu homozygotes showed a reduction of alpha- and beta-cells to 59 and 61%, respectively, pancreatic endocrine development was unaltered in the Pax6132-14Neu mutant strain.
conclusionsWe show that inactivation of the Pax6 paired domain leads to a more severe phenotype with regards to the differentiation of pancreatic alpha-cells than the loss of the transactivation domain. The analysis of two different homeodomain mutants suggests that the binding of Pax6 to P3 homeodomain consensus sequences is not required for alpha-cell development. It rather seems that the homeodomain has a modulating role in Pax6 function, possibly by facilitating a PH0-like binding confirmation on paired domain target genes like proglucagon. This function is differentially affected by the two homeodomain mutations analyzed in this study.
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