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Cell Cycle Arrest of a ‘Zippering’ Epithelial Cell Cluster Mediates Face Morphogenesis in Mice and Humans and is Unleashed in Craniofacial Disorders [scRNA-seq]

GSE299536 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/06/11 Platform GPL34328
Summary
Facial features identify individuals, but the mechanisms shaping the human face remain elusive. Orofacial clefting (OFC), the most common craniofacial abnormality, results from failed fusion of the facial prominences, partly caused by persistence of the cephalic epithelium. Using mouse models to guide our studies, here we uncover the identity, behaviors, and molecular blueprints of a novel craniofacial epithelial population, Zippering Lambda (ZL), similarly characterized by cell cycle arrest in mouse and human embryos. Remarkably, in Pbx1/2 and p63 mutant mice with OFC cell cycle is unleashed in ZL epithelium. Intersecting ZL-enriched genes with human OFC whole-genome sequencing datasets identifies ZFHX3 variants in affected individuals and cephalic epithelial Zfhx3 deletion results in murine OFC. Our findings further demonstrate that ZFHX3 and PBX1 synergistically regulate cell cycle inhibitor genes acting within a complex in embryonic faces. Collectively, we deconstruct new mechanisms that pattern the face, connecting cell cycle arrest to developmental tissue fusion.
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Direct links to NCBI, no account and no request form: the whole study as GSE299536_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1274926 and SRA study SRP591468. Searching any of these in the dataset finder brings you back here.

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