Abstract
Cranial sutures are essential for skull growth and tissue homeostasis. Among them, the coronal suture is most frequently affected in syndromic craniosynostosis, yet the mechanisms underlying this preferential involvement remain unclear. Here, we show that the coronal suture mesenchyme undergoes a postnatal lineage transition from mesodermal to cranial neural crest origin, facilitated by dural cell migration into the suture. Mechanistically, this migration is regulated by suture TGFβ signals to Tgfbr2+ dural cells. Loss of dural Tgfbr2 impairs this cell migration into the suture, reduces the Gli1+ suture progenitor pool, and causes premature coronal suture fusion. Furthermore, in Twist1+/- mice recapitulating human Saethre-Chotzen syndrome, upregulated decorin leads to compromised TGFβ signaling, which impairs dural cell migration, leading to craniosynostosis. Significantly, restoring TGFβ signaling rescues coronal suture patency in Twist1+/- mice. These findings identify the critical role of TGFβ-mediated dural-suture interactions, particularly dural cell migration, in maintaining coronal suture patency and provide an explanation for the preferential coronal fusion in syndromic craniosynostosis.
Acknowledgements
We gratefully acknowledge Bridget Samuels, Kimi Nakaki, and Linda Hattemer (Center for Craniofacial Molecular Biology, USC) for their critical review of the manuscript. We thank Drs. Robert Maxson and Pedro Sanchez for Twist1+/− mice and discussion. We thank Ivetta Vorobyova (Molecular Imaging Center, USC) for all the live micro-CT scanning. This work was supported by the National Institute of Dental and Craniofacial Research, National Institutes of Health (NIDCR/NIH R01 DE0030901 to Y.C.).
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Chen, P., Meng, L., Lan, L. et al. TGFβ-mediated dural progenitor cell migration into the coronal suture is crucial for preventing craniosynostosis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73292-w
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DOI: https://doi.org/10.1038/s41467-026-73292-w