Med23 Regulates Sox9 Expression during Craniofacial Development
| Autor: | Shachi Bhatt, K T Falcon, Soma Dash, Lisa L. Sandell, Paul A. Trainor |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
animal structures Mesenchyme SOX9 Biology Mesoderm Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Craniofacial Wnt Signaling Pathway General Dentistry Mediator Complex Pierre Robin Syndrome Glossoptosis Wnt signaling pathway Neural crest SOX9 Transcription Factor Research Reports Phenotype Cell biology Cleft Palate 030104 developmental biology medicine.anatomical_structure Neural Crest embryonic structures medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | J Dent Res |
| ISSN: | 1544-0591 0022-0345 |
| DOI: | 10.1177/0022034520969109 |
| Popis: | The etiology and pathogenesis of craniofacial birth defects are multifactorial and include both genetic and environmental factors. Despite the identification of numerous genes associated with congenital craniofacial anomalies, our understanding of their etiology remains incomplete, and many affected individuals have an unknown genetic diagnosis. Here, we show that conditional loss of a Mediator complex subunit protein, Med23 in mouse neural crest cells ( Med23 fx/fx; Wnt1-Cre), results in micrognathia, glossoptosis, and cleft palate, mimicking the phenotype of Pierre Robin sequence. Sox9 messenger RNA and protein levels are both upregulated in neural crest cell–derived mesenchyme surrounding Meckel’s cartilage and in the palatal shelves in Med23 fx/fx; Wnt1-Cre mutant embryos compared to controls. Consistent with these observations, we demonstrate that Med23 binds to the promoter region of Sox9 and represses Sox9 expression in vitro. Interestingly, Sox9 binding to β-catenin is enhanced in Med23 fx/fx; Wnt1-Cre mutant embryos, which, together with downregulation of Col2a1 and Wnt signaling target genes, results in decreased proliferation and altered jaw skeletal differentiation and cleft palate. Altogether, our data support a cell-autonomous requirement for Med23 in neural crest cells, potentially linking the global transcription machinery through Med23 to the etiology and pathogenesis of craniofacial anomalies such as micrognathia and cleft palate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|