Cleft lip with/without cleft palate is one of the most common congenital birth defects in humans worldwide. The development of cleft lip is influenced by complex multiple genetic and environmental factors. Recent studies reveal that epigenetic factors affect gene expression and phenotype without altering DNA sequence and contribute to a number of birth defects and diseases. MicroRNAs (miRs), one of these epigenetic factors, target ~30% of protein-coding genes, and each miR functions to repress several targets. Having been implicated in a wide range of physiological and pathological conditions, miRs may be expressed in a temporal and spatial specific manner during lip formation. However, it is still largely unknown which and how miRs are essential for lip development. We hypothesize that the proper control of miRs is crucial for the regulation of genes that play important roles in lip development and that its disruption causes cleft lip. To identify miRs involved in lip development, we will analyze miR-seq and mRNA microarray datasets from the mouse developing lip region, as well as human genotype-phenotype and cleft lip case-parent trio data provided by a FaceBase1 project. We will further define expression levels, patterns, and functions of these miRs experimentally.
Our specific aims are to 1) identify miRs involved in cleft lip; and 2) identify target genes regulated by miRs during lip development. This study will provide insights into the role of miRs in lip development and suggest possible strategies for the diagnosis and prevention of cleft lip.
The etiology of cleft lip is complicated, with a variety of genetic and environmental factors involved. This study will identify the contribution of microRNAs (miRs), which are regulated by environmental factors, in lip development. The results of this study will facilitate our understanding of the role of miRs in lip development and will enable us to design future diagnostic and therapeutic approaches to prevent cleft lip.
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