Progenitor and stem cell dysfunction is at the center of many congenital disorders. Despite their clinical relevance, we still know little, however, about the cellular and molecular mechanisms that establish and maintain long-living stem cells. In humans with a common birth defect called craniosynostosis, these skeletal stem cells are lost, leading to premature bone fusions, and as a result, a heightened risk of impaired brain development. While genetic studies have identified many mutations that lead to craniosynostosis, the origin of skeletal stem cells and their interacting cell types in the suture remain unclear. My work integrates mice and zebrafish to interrogate the behavior of skeletal stem cells that reside within the sutures. By performing scRNA-seq of the mouse and zebrafish coronal suture during developmental stages, I have uncovered a rich diversity of mesenchymal cell types that reside within and around the coronal suture including a novel population of skeletal progenitors. I have demonstrated that these skeletal progenitors are selectively depleted in a model of craniosynostosis, strengthening the argument that stem cell and progenitor dysfunction are critical drivers of suture loss. My current research focuses on the intra-cellular and biomechanical inputs that control skeletal stem cells under heathy and pathological conditions.