ArticleThe Journal of biological chemistry2013
The LIM homeodomain transcription factor LHX6: a transcriptional repressor that interacts with pituitary homeobox 2 (PITX2) to regulate odontogenesis.
Article in The Journal of biological chemistry, 2013. 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.
- CREATE: cell-type-specific cis-regulatory element identification via discrete embedding.Nature communications · 2025Article
- Lhx6 deficiency causes human embryonic palatal mesenchymal cell mitophagy dysfunction in cleft palate.Molecular medicine (Cambridge, Mass.) · 2024Article
- Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development.Nature neuroscience · 2024Article
- Overlapping Interstitial Deletions of the Region 9q22.33 to 9q33.3 of Three Patients Allow Pinpointing Candidate Genes for Epilepsy and Cleft Lip and Palate.Molecular syndromology · 2023Article
- Homeobox Genes in Odontogenic Lesions: A Scoping Review.Head and neck pathology · 2023Article
- Lhx6 regulates canonical Wnt signaling to control the fate of mesenchymal progenitor cells during mouse molar root patterning.PLoS genetics · 2021Article
- LHX6 Affects Erlotinib Resistance and Migration ofOncoTargets and therapy · 2020Article
- Genomic imbalances defining novel intellectual disability associated loci.Orphanet journal of rare diseases · 2019Article
- FoxO6 regulates Hippo signaling and growth of the craniofacial complex.PLoS genetics · 2018Article
- ALX4, an epigenetically down regulated tumor suppressor, inhibits breast cancer progression by interfering Wnt/β-catenin pathway.Journal of experimental & clinical cancer research : CR · 2017Article
- Advances and perspectives in tooth tissue engineering.Journal of tissue engineering and regenerative medicine · 2017Review
- Cellular and molecular mechanisms of tooth root development.Development (Cambridge, England) · 2017Review
- LHX6, An Independent Prognostic Factor, Inhibits Lung Adenocarcinoma Progression through Transcriptional Silencing of β-catenin.Journal of Cancer · 2017Article
- Modulation of light-driven arousal by LIM-homeodomain transcription factor Apterous in large PDF-positive lateral neurons of the Drosophila brain.Scientific reports · 2016Article
- Lhx6 and Lhx8: cell fate regulators and beyond.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Review
- Identification of a face enhancer reveals direct regulation of LIM homeobox 8 (Lhx8) by wingless-int (WNT)/β-catenin signaling.The Journal of biological chemistry · 2014Article
- On the cutting edge of organ renewal: Identification, regulation, and evolution of incisor stem cells.Genesis (New York, N.Y. : 2000) · 2014Review
- A model for the molecular underpinnings of tooth defects in Axenfeld-Rieger syndrome.Human molecular genetics · 2014Article
- LHX6 acts as a novel potential tumour suppressor with epigenetic inactivation in lung cancer.Cell death & disease · 2013Article
- Whole-genome mRNA expression profiling identifies functional and prognostic signatures in patients with mesenchymal glioblastoma multiforme.CNS neuroscience & therapeutics · 2013Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
LHX6 is a LIM-homeobox transcription factor expressed during embryogenesis; however, the molecular mechanisms regulating LHX6 transcriptional activities are unknown. LHX6 and the PITX2 homeodomain transcription factor have overlapping expression patterns during tooth and craniofacial development, and in this report, we demonstrate new transcriptional mechanisms for these factors. PITX2 and LHX6 are co-expressed in the oral and dental epithelium and epithelial cell lines. Lhx6 expression is increased in Pitx2c transgenic mice and decreased in Pitx2 null mice. PITX2 activates endogenous Lhx6 expression and the Lhx6 promoter, whereas LHX6 represses its promoter activity. Chromatin immunoprecipitation experiments reveal endogenous PITX2 binding to the Lhx6 promoter. LHX6 directly interacts with PITX2 to inhibit PITX2 transcriptional activities and activation of multiple promoters. Bimolecular fluorescence complementation assays reveal an LHX6·PITX2 nuclear interaction in living cells. LHX6 has a dominant repressive effect on the PITX2 synergistic activation with LEF-1 and β-catenin co-factors. Thus, LHX6 acts as a transcriptional repressor and represses the expression of several genes involved in odontogenesis. We have identified specific defects in incisor, molar, mandible, bone, and root development and late stage enamel formation in Lhx6 null mice. Amelogenin and ameloblastin expression is reduced and/or delayed in the Lhx6 null mice, potentially resulting from defects in dentin deposition and ameloblast differentiation. Our results demonstrate that LHX6 regulates cell proliferation in the cervical loop and promotes cell differentiation in the anterior region of the incisor. We demonstrate new molecular mechanisms for LHX6 and an interaction with PITX2 for normal craniofacial and tooth development.
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