The developing mouse coronal suture at single-cell resolution.

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Publication Year:
2021
Authors:
D'Juan T Farmer, Hana Mlcochova, Yan Zhou, Nils Koelling, Guanlin Wang, Neil Ashley, Helena Bugacov, Hung-Jhen Chen, Riana Parvez, Kuo-Chang Tseng, Amy E Merrill, Robert E Jr Maxson, Andrew O M Wilkie, J Gage Crump, Stephen R F Twigg
PubMed ID:
34376651
Funding Grants:
Public Summary:
This study explores the development of the coronal suture, which is a critical structure that separates the flat bones of the skull, allowing for coordinated growth of the brain and the skull. This suture is frequently fused in craniosynostosis, a condition primarily caused by genetic factors. To understand the cellular diversity within the coronal suture during mouse embryonic development, researchers used single-cell analysis. The authors discovered different groups of cells, including those with characteristics of pre-osteoblasts (bone-forming cells), ligament-like cells above the suture that persist into adulthood, and chondrogenic-like cells in the dura mater beneath the suture. Additionally, they identified a population of embryonic osteoprogenitor cells contributing to the postnatal suture mesenchyme. Understanding these cellular components and their roles is crucial for gaining insights into the development of the coronal suture and the mechanisms behind its fusion in conditions like craniosynostosis.
Scientific Abstract:
Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet the unique aspects of its development remain incompletely understood. To uncover the cellular diversity within the murine embryonic coronal suture, we generated single-cell transcriptomes and performed extensive expression validation. We find distinct pre-osteoblast signatures between the bone fronts and periosteum, a ligament-like population above the suture that persists into adulthood, and a chondrogenic-like population in the dura mater underlying the suture. Lineage tracing reveals an embryonic Six2+ osteoprogenitor population that contributes to the postnatal suture mesenchyme, with these progenitors being preferentially affected in a Twist1+/-; Tcf12+/- mouse model of Saethre-Chotzen Syndrome. This single-cell atlas provides a resource for understanding the development of the coronal suture and the mechanisms for its loss in craniosynostosis.