Facial morphology is influenced by a genetic basis with a wide array of variations. In severe cases, the morphological changes are recognized as frontonasal anomalies, malformations characterized by hypertelorism (an increased distance between the eyes), a flat broad nose, malformed nasal tip, a vertical groove down the middle of the face, etc. The etiology of frontonasal anomalies is complex with multiple genetic and environmental factors. Recent studies suggest that microRNAs (miRs), short non-coding RNAs regulated by environmental cues, can repress multiple target genes (~30% of protein-coding genes) and contribute to a number of diseases and developmental disorders. We hypothesize that the proper control of miR expression is crucial for the regulation of genes involved in frontonasal development. In this study, we will identify miRs highly expressed in the frontonasal region during craniofacial development by analyzing RNA-seq datasets from the mouse developing frontonasal region. We will also identify target genes regulated by miRs during frontonasal development by analyzing miR-mRNA anti-correlation. We will further test the genotype-phenotype associations of these candidate miRs and genes using public available datasets from genome-wide studies. These findings will be validated in our confirmative experiments. Taken together, this study will provide insights into the role of miRs in frontonasal development and suggest possible strategies for the diagnosis and prevention of frontonasal anomalies.

Public Health Relevance

This study will provide a better understanding of facial variations and frontonasal anomalies as well as data that will be available for future research of mouse genetic approaches used to characterize the individual or cluster microRNAs (miRs) identified in this proposal. This study will yield important insights into miR function in frontonasal development and will provide new opportunities to investigate the complex genetic and epigenetic networks underlying facial morphogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE028340-01
Application #
9647521
Study Section
Special Emphasis Panel (ZDE1)
Program Officer
Khatipov, Emir A
Project Start
2019-02-01
Project End
2021-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Other Basic Sciences
Type
Schools of Dentistry/Oral Hygn
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77030