The role of embryonic origins and suture proximity in repair of cranial bone

The cranial sutures are proposed to be a stem cell niche, harbouring skeletal stem cells (SSCs) that are directly involved in development, homeostasis, and healing. Like the craniofacial bones, the sutures are formed from both mesoderm and neural crest. During cranial repair, neural crest cells have been proposed to be key players; however, neural crest contributions to the sutures are not well defined, and the relative importance of suture proximity is unclear. Here, we combine calvarial wounding experiments with genetically labelled mouse models to demonstrate that suture proximity predicts the efficiency of cranial repair. Furthermore, we define the neural crest-mesoderm boundary within the sutures and demonstrate that Gli1+ and Axin2+ SSCs are present in all calvarial sutures examined. We propose that the position of the defect determines the availability of neural crest-derived progenitors, which appear to be a key element in the repair of calvarial defects. Summary statement This study provides a new examination of the embryonic origins of cranial sutures in mouse. Using genetic lineage labelling, we identify specific contributions of neural crest cells and associated skeletal stem cells during repair of calvarial wounds. This is extremely relevant considering recent findings regarding the role of suture-residing stem cells.