Disruption of Irf6-dependent periderm differentiation during palatogenesis correlates with the occurrence of a myoepithelial-like surface ectoderm cell population
Year: 2026
Type: dataset
Abstract: Orofacial clefts (OFCs) are among the most common structural birth conditions, and the transcription factor IRF6 is associated with both syndromic and isolated cleft lip and palate. The Irf6 null mouse model exhibits severe epithelial adhesions globally, with under-developed midface, cleft of the secondary palate and defective limb development. However, a detailed analysis of the development of the primary palate, a region termed the lambdoid junction, has not been fully described in the Irf6 mutant. Here we performed a detailed histological analysis and single-nucleus RNA sequencing of the craniofacial prominences, including the lambdoid junction, in Irf6-/- and wildtype mice. We found that at E11.5 Irf6-/- embryos exhibit structural changes to the craniofacial prominences, with epithelial cell composition and morphological differences within the lambdoid junction. These findings were reflected in the RNA sequencing results, where Irf6-/- embryos lacked periderm and developed an aberrant myoepithelial-like cell type that lined the surface of the craniofacial prominences, the oral cavity, and developing limbs. These findings provide new understanding of epithelial cell development may that underpin cleft malformation and identifies pathways that may be tractable in future therapeutic approaches.
Institution: Children's Hospital of Philadelphia
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213237127
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