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A groundbreaking study led by the University of Wisconsin School of Veterinary Medicine sheds light on the development of orofacial clefts, including cleft lip and palate, in mice. The study, published in the Proceedings of the National Academy of Sciences (PNAS), reveals the crucial role of DNA methylation—a process altering gene expression without changing DNA sequence—in craniofacial development.

The researchers, led by Associate Professor Robert Lipinski, manipulated DNA methylation in mouse embryos, establishing a direct link between disruptions in this process and the development of cleft lip and palate. This discovery is a vital step toward understanding the environmental factors contributing to these birth defects, which affect over 175,000 newborns worldwide annually.

Lipinski’s team identified a specific gestational day during embryonic development—equivalent to the beginning of the fifth week in humans—when DNA methylation disruptions led to orofacial clefts in mice. This narrow window of sensitivity highlights the importance of timing in the developmental process.

The study’s findings open avenues for preventive strategies, potentially reducing the risk of orofacial clefts in both animals and humans. Lipinski emphasized the role of DNA methylation as influenced by various environmental factors, including maternal stress, diet, drugs, toxins, and pollutants.

To further their research, the team developed a new in vitro model allowing rapid screening of thousands of dietary and environmental factors in a laboratory dish. This model will facilitate the identification of factors influencing cleft susceptibility, expediting the understanding of modifiable risk factors.

Orofacial clefts, affecting approximately 1 in 700 newborns, pose challenges such as feeding difficulties, multiple surgeries, dental procedures, and speech therapy. The study’s outcomes provide a foundation for future research focused on specific environmental factors influencing DNA methylation during orofacial development.

The study received support from the National Institutes of Health and the University of Wisconsin Hilldale Undergraduate Research Award. This breakthrough offers hope for advancing birth defect prevention strategies and improving the lives of those affected by orofacial clefts.

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