MicroRNAs as epigenetic regulators of orofacial development.

Area of Science:

• Developmental Biology
• Genetics
• Epigenetics

Background:

• Orofacial clefts are common congenital craniofacial malformations influenced by environmental and genetic factors.
• Epigenetics, especially microRNAs (miRNAs), is increasingly recognized as a fundamental process in embryogenesis and development.
• Environmental factors impacting embryonic development are often mediated through the epigenome.

Purpose of the Study:

• To review the role of microRNAs (miRNAs) in lip and palate morphogenesis.
• To summarize studies identifying miRNAs involved in orofacial cleft development.
• To highlight the potential of miRNA-target gene interactions in understanding cleft etiology.

Main Methods:

• Review of existing literature on miRNAs and orofacial clefting.
• Analysis of studies involving gene knockouts (Dicer, DGCR8) in neural crest cells.
• Examination of identified miRNA-target gene interactions in lip and palate development.

Main Results:

• Conditional knockouts of miRNA machinery genes (Dicer, DGCR8) in neural crest cells lead to craniofacial anomalies, including cleft lip and palate.
• miRNAs regulate key morphogenetic processes such as apoptosis, cell proliferation, differentiation, and epithelial-mesenchymal transition (EMT).
• Numerous miRNA-target gene interactions implicated in orofacial clefts have been identified, though many require functional validation.

Conclusions:

• Epigenetic pathways, particularly miRNAs, are vital regulators of gene expression during orofacial embryogenesis.
• Aberrant miRNA expression and function are significant contributors to the etiology of orofacial clefts.
• Further research into validated miRNA-target gene interactions holds promise for novel therapeutic strategies for clefting disorders.