What is it about?

Clefts of the lip and palate are among the most common human birth defects and thought to result from complex gene-environment interactions. We examined the role of an environmentally sensitive epigenetic mechanism in orofacial development.

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Why is it important?

Our work shows that DNA methylation regulates orofacial development and that its disruption during an early embryonic window of sensitivity results in OFCs in mice. We demonstrate that this epigenetic mechanism is required for proliferation and differentiation of stem cells that form orofacial connective tissue and that the cellular mechanisms of orofacial cleft pathogenesis can be recapitulated in a tractable in vitro model.


These studies provide new conceptual insight and experimental platforms for understanding how an environmentally malleable epigenetic mechanism could be harnessed to advance prevention strategies that could reduce the incidence of these birth defects.

Robert Lipinski
University of Wisconsin Madison

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This page is a summary of: Disruption of DNA methylation–mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice, Proceedings of the National Academy of Sciences, January 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2317668121.
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