Project Grant R56DE030917

This Project Grant from the National Institutes of Health's National Institute of Dental and Craniofacial Research will fund $876,704 in research into DNA methylation's role in orofacial clefting. Led by the University of Wisconsin-Madison from August 2022 to August 2023, the project aims to advance understanding of epigenetic mechanisms in birth defects through several integrated studies. Researchers will apply genome-wide methylation and single-cell transcriptome approaches to a novel mouse model where orofacial clefts result from cranial neural crest DNA methylation disruption. They will also define DNA methylation's role in multifactorial cleft susceptibility by integrating multiple environmental and dietary modulators into genetic and chemical mouse models of incompletely penetrant clefts. Insights into how DNA methylation regulates cranial neural crest biology and orofacial morphogenesis may inform future work interrogating specific methylation events. Study results are expected to advance the long-term goal of developing prevention strategies for etiologically complex birth defects by identifying culpable environmental influences and their mechanisms of action.