ArticleProceedings of the National Academy of Sciences of the United States of America2002
Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6 haploinsufficient lens phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 88 citations in OpenAlex.
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- Making a head: Neural crest and ectodermal placodes in cranial sensory development.Seminars in cell & developmental biology · 2023Review
- Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation.Epigenetics & chromatin · 2023Article
- Study on the Correlation Between Iris Characteristics and Schizophrenia.Neuropsychiatric disease and treatment · 2022Article
- The SIX Family of Transcription Factors: Common Themes Integrating Developmental and Cancer Biology.Frontiers in cell and developmental biology · 2021Review
- The Spectrum ofGenes · 2019Review
- The genetic architecture of aniridia and Gillespie syndrome.Human genetics · 2019Review
- PAX6 can substitute for LHX2 and override NFIA-induced astrogliogenesis in developing hippocampus in vivo.Journal of biosciences · 2018Article
- The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6.PLoS genetics · 2016Article
- A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish.The Journal of biological chemistry · 2015Article
- The cellular and molecular mechanisms of vertebrate lens development.Development (Cambridge, England) · 2014Review
- Article
- Systematic analysis of palatal transcriptome to identify cleft palate genes within TGFβ3-knockout mice alleles: RNA-Seq analysis of TGFβ3 Mice.BMC genomics · 2013Article
- Ocular surface development and gene expression.Journal of ophthalmology · 2013Article
- Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways.Breast cancer research : BCR · 2012Article
- Wnt/β-catenin signaling and Msx1 promote outgrowth of the maxillary prominences.Frontiers in physiology · 2012Article
- Candidate gene screen in the red flour beetle Tribolium reveals six3 as ancient regulator of anterior median head and central complex development.PLoS genetics · 2011Article
- Tumor suppressor PAX6 functions as androgen receptor co-repressor to inhibit prostate cancer growth.The Prostate · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Pax6 is a key regulator of eye development in vertebrates and invertebrates, and heterozygous loss-of-function mutations of the mouse Pax6 gene result in the Small eye phenotype, in which a small lens is a constant feature. To provide an understanding of the mechanisms underlying this haploinsufficient phenotype, we evaluated in Pax6 heterozygous mice the effects of reduced Pax6 gene dosage on the activity of other transcription factors regulating eye formation. We found that Six3 expression was specifically reduced in lenses of Pax6 heterozygous mouse embryos. Interactions between orthologous genes from the Pax and Six families have been identified in Drosophila and vertebrate species, and we examined the control of Pax6 and Six3 gene expression in the developing mouse lens. Using in vitro and transgenic approaches, we found that either transcription factor binds regulatory sequences from the counterpart gene and that both genes mutually activate their expression. These studies define a functional relationship in the lens in which Six3 expression is dosage-dependent on Pax6 and where, conversely, Six3 activates Pax6. Accordingly, we show a rescue of the Pax6 haploinsufficient lens phenotype after lens-specific expression of Six3 in transgenic mice. This phenotypic rescue was accompanied by cell proliferation and activation of the platelet-derived growth factor alpha-R/cyclin D1 signaling pathway. Our findings thus provide a mechanism implicating gene regulatory interactions between Pax6 and Six3 in the tissue-specific defects found in Pax6 heterozygous mice.
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