ArticleDevelopmental biology2010
Tbx1 regulates progenitor cell proliferation in the dental epithelium by modulating Pitx2 activation of p21.
Article in Developmental biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Transcriptional programs of Pitx2 and Tfap2a/Tfap2b controlling lineage specification of mandibular epithelium during tooth initiation.PLoS genetics · 2024Article
- Article
- Decoding the PITX2-controlled genetic network in atrial fibrillation.JCI insight · 2022Article
- Craniofacial Phenotypes and Genetics of DiGeorge Syndrome.Journal of developmental biology · 2022Review
- The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis.Cancers · 2021Review
- New insight into dental epithelial stem cells: Identification, regulation, and function in tooth homeostasis and repair.World journal of stem cells · 2020Review
- Article
- Identification of Deregulated Pathways, Key Regulators, and Novel miRNA-mRNA Interactions in HPV-Mediated Transformation.Cancers · 2020Article
- FoxO6 regulates Hippo signaling and growth of the craniofacial complex.PLoS genetics · 2018Article
- The Role of Fibroblast Growth Factors in Tooth Development and Incisor Renewal.Stem cells international · 2018Review
- p27Oncogene · 2017Article
- Coevolutionary patterning of teeth and taste buds.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- TBX1 protein interactions and microRNA-96-5p regulation controls cell proliferation during craniofacial and dental development: implications for 22q11.2 deletion syndrome.Human molecular genetics · 2015Article
- Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2.Experimental cell research · 2015Article
- Lhx4 deficiency: increased cyclin-dependent kinase inhibitor expression and pituitary hypoplasia.Molecular endocrinology (Baltimore, Md.) · 2015Article
- A case of 22q11.2 deletion syndrome with Peters anomaly, congenital glaucoma, and heterozygous mutation in CYP1B1.Ophthalmic genetics · 2015Article
- A pituitary homeobox 2 (Pitx2):microRNA-200a-3p:β-catenin pathway converts mesenchymal cells to amelogenin-expressing dental epithelial cells.The Journal of biological chemistry · 2014Article
- p53 Suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- On the cutting edge of organ renewal: Identification, regulation, and evolution of incisor stem cells.Genesis (New York, N.Y. : 2000) · 2014Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Tbx1(-/-) mice present with phenotypic effects observed in DiGeorge syndrome patients however, the molecular mechanisms of Tbx1 regulating craniofacial and tooth development are unclear. Analyses of the Tbx1 null mice reveal incisor microdontia, small cervical loops and BrdU labeling reveals a defect in epithelial cell proliferation. Furthermore, Tbx1 null mice molars are lacking normal cusp morphology. Interestingly, p21 (associated with cell cycle arrest) is up regulated in the dental epithelium of Tbx1(-/-) embryos. These data suggest that Tbx1 inhibits p21 expression to allow for cell proliferation in the dental epithelial cervical loop, however Tbx1 does not directly regulate p21 expression. A new molecular mechanism has been identified where Tbx1 inhibits Pitx2 transcriptional activity and decreases the expression of Pitx2 target genes, p21, Lef-1 and Pitx2c. p21 protein is increased in PITX2C transgenic mouse embryo fibroblasts (MEF) and chromatin immunoprecipitation assays demonstrate endogenous Pitx2 binding to the p21 promoter. Tbx1 attenuates PITX2 activation of endogenous p21 expression and Tbx1 null MEFs reveal increased Pitx2a and activation of Pitx2c isoform expression. Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 transcriptional activation of the p21, LEF-1, and Pitx2c promoters. Tbx1(-/+)/Pitx2(-/+) double heterozygous mice present with an extra premolar-like tooth revealing a genetic interaction between these factors. The ability of Tbx1 to repress PITX2 activation of p21 may promote cell proliferation. In addition, PITX2 regulation of p21 reveals a new role for PITX2 in repressing cell proliferation. These data demonstrate new functional mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for craniofacial defects in DiGeorge syndrome patients.
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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.