The stem cells (green), found in the early postnatal coronal suture, are responsible for separating and growing neighboring bones (magenta). Credit: D'Juan Farmer/Crump Lab/USC Stem CellContrary to popular belief, the neck bone actually connects to one of the 22 head bones that make the human skull. These plates-like bones are connected at special joints called sutures. They allow the skull to expand with brain growth, but they are missing in children born with craniosynostosis. Nature Communications has published a new study that provides a detailed cell atlas of coronal sutures in development. This is the most common type of fusion due to single gene mutations. Researchers from Gage Crump's Robert Maxson and Amy Merrill at USC as well as Andrew Wilkie at Oxford and Stephen Twigg at University of Oxford contributed to the study.D'Juan Farmer (a Crump Lab postdoctoral fellow), led the research. "Named after its location at crown of the skull, the coronal stitch is affected in many birth defects," he said. These children and infants must undergo a series invasive and risky surgeries to expand their skulls. We wanted to find out why the coronal susture is so sensitive to gene disruptions. We created the first cell-by-cell detailed description of how this suture is made in an effort to advance new treatments for patients.Farmer and his colleagues isolated cells from developing coronal sutures in mice to achieve this. To catalog the activity of every protein-coding gene in thousands of cells, the team used advanced DNA sequencing techniques.They were able identify 14 different types of cells within and around the suture by using unique fingerprints of gene activation. They also discovered new genes that could be involved in the generation and maintenance of the stem cells that produce the skull bones.The embryonic coronal suture gives rise to stem cells (red), which are embedded in the bone matrix (green). Credit: DJuan Farmer/Crump Lab/USC Stem CellScientists discovered many cell types in the tissue connecting skull bones and underlying brain that could communicate with the suture stem cells. This may allow them to regulate their activity. Scientists also discovered ligament-like cells overlying the skull plates that can be sustained into adulthood. These ligament-like cells can be stretched by the brain and could indicate to bone precursors nearby that it is time to expand the skull.To understand the effects of different cell types, scientists looked at a mouse model that was affected by a specific form of craniosynostosis called Saethre-Chotzen Syndrome. The distribution of suture stem cells in healthy mice was asymmetrical. This is likely to explain a unique feature in the coronal suture, which is the overlap of the skull plates. Conversely, mice with craniosynostosis had fewer suture stem cell and were more symmetrically distributed. This could cause the skull plates' edges to grow into one another and lead to suture fusions.Farmer stated, "By studying the very early stages of coronal stitch development at cellular resolution our study provides key insight into why this suture can be particularly vulnerable to defects for newborns with craniosynostosis." We hope these findings will inform more invasive and even preventive treatments for infants with this fatal birth defect.Continue exploring Zebrafish are making waves in our understandings of a common craniofacial defectInformation: D'Juan T. Farmer et. al., The developing mouse coronal susture at single cell resolution, Nature Communications (2021). Information from Nature Communications D'Juan T. Farmer and colleagues, The developing mouse coronal susture at single cell resolution, (2021). DOI: 10.1038/s41467-021-24917-9
