Abstract:
: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.
journal_name
J Dent Resjournal_title
Journal of dental researchauthors
Dash S,Bhatt S,Falcon KT,Sandell LL,Trainor PAdoi
10.1177/0022034520969109subject
Has Abstractpub_date
2020-11-06 00:00:00pages
22034520969109eissn
0022-0345issn
1544-0591pub_type
杂志文章abstract::The effect of toothbrushes on soft tissue abrasion was measured using hamster cheek pouch tissue brushed mechanically for various intervals. The detection of protein removed during brushing was used as an index of tissue abrasion. The method was found to be sensitive in detecting the effects of brush load, number of s...
journal_title:Journal of dental research
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