Oral lining mucosa development depends on mesenchymal microRNAs
Y Otsuka-Tanaka1, S Oommen, M Kawasaki
1Craniofacial Development and Stem Cell Biology, and Biomedical Research Centre, Dental Institute, King's College London, Guy's Hospital, London Bridge, London SE1 9RT, UK.
Abstract:
The oral mucosa plays critical roles in protection, sensation, and secretion and can be classified into masticatory, lining, and specialized mucosa that are known to be functionally, histologically, and clinically distinct. Each type of oral mucosa is believed to develop through discrete molecular mechanisms, which remain unclear. MicroRNAs (miRNAs) are 19 to 25nt non-coding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs. miRNAs are crucial for fine-tuning of molecular mechanisms. To investigate the role of miRNAs in oral mucosa development, we examined mice with mesenchymal (Wnt1Cre;Dicer(fl/fl)) conditional deletion of Dicer. Wnt1Cre;Dicer(fl/fl) mice showed trans-differentiation of lining mucosa into an epithelium with masticatory mucosa/ skin-specific characteristics. Up-regulation of Fgf signaling was found in mutant lining mucosal epithelium that was accompanied by an increase in Fgf7 expression in mutant mesenchyme. Mesenchyme miRNAs thus have an indirect effect on lining mucosal epithelial cell growth/differentiation.
Insights
Mesenchymal microRNAs (miRNAs) influence oral mucosa development. Conditional deletion of Dicer in mice caused lining mucosa to transform into masticatory-like epithelium, revealing miRNA
Area of Science:
- Developmental Biology
- Molecular Biology
- Oral Biology
Background:
- The oral mucosa, comprising masticatory, lining, and specialized types, has distinct functions and development.
- Molecular mechanisms underlying oral mucosa differentiation are not fully understood.
- MicroRNAs (miRNAs) are key regulators of gene expression, crucial for fine-tuning developmental processes.
Purpose of the Study:
- To investigate the role of mesenchymal microRNAs (miRNAs) in oral mucosa development.
- To elucidate the molecular pathways involved in the differentiation of oral mucosal tissues.
Main Methods:
- Utilized a mouse model with conditional deletion of Dicer in the Wnt1-expressing mesenchymal cells (Wnt1Cre;Dicer(fl/fl)).
- Analyzed the histological and molecular characteristics of the oral mucosa in mutant mice.
- Examined gene expression patterns, focusing on Fibroblast Growth Factor (FGF) signaling.
Main Results:
- Mesenchymal Dicer deletion led to the trans-differentiation of lining mucosa into an epithelium resembling masticatory mucosa and skin.
- Upregulation of FGF signaling was observed in the mutant lining mucosal epithelium.
- Increased Fgf7 expression in the mutant mesenchyme suggests an indirect role of mesenchymal miRNAs in epithelial cell regulation.
Conclusions:
- Mesenchymal microRNAs play a critical, albeit indirect, role in regulating the growth and differentiation of oral lining mucosal epithelium.
- Disruption of miRNA processing in the mesenchyme can induce significant changes in oral mucosal tissue characteristics.
- FGF signaling is implicated as a downstream pathway affected by mesenchymal miRNA dysregulation in oral mucosa development.
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