biostudies-literatureEyal SDavid and Fela Shapell Family Foundation INCPM Fund for Preclinical StudiesDavid and Fela Shapell Family Center for Genetic DisordersJaffe Bernard and Audrey FoundationEuropean Research CouncilNational Institutes of HealthNIAMS NIH HHSJeanne and Joseph Nissim Foundation for Life Sciences ResearchY. Leon Benoziyo Institute for Molecular Medicinedev167882https://www.ebi.ac.uk/biostudies/studies/S-EPMC6679367biostudies-literatureUnknown146(14)Bone protrusions provide stable anchoring sites for ligaments and tendons and define the unique morphology of each long bone. Despite their importance, the mechanism by which superstructures are patterned is unknown. Here, we identify components of the genetic program that control the patterning of <i>Sox9</i>⁺/<i>Scx</i>⁺ superstructure progenitors in mouse and show that this program includes both global and regional regulatory modules. Using light-sheet fluorescence microscopy combined with genetic lineage labeling, we mapped the broad contribution of the <i>Sox9</i>⁺/<i>Scx</i>⁺ progenitors to the formation of bone superstructures. Then, by combining literature-based evidence, comparative transcriptomic analysis and genetic mouse models, we idDevelopment (Cambridge, England)Bone morphology is regulated modularly by global and regional genetic programs.PMC6679367R01 AR061402R01 AR055580310098Krief SWellik DMPineault KMEyal SFelsenthal NAddadi YSalame TMKult SZelzer ERubin SLeshkowitz DfalseBone morphology is regulated modularly by global and regional genetic programs.Bone protrusions provide stable anchoring sites for ligaments and tendons and define the unique morphology of each long bone. Despite their importance, the mechanism by which superstructures are patterned is unknown. Here, we identify components of the genetic program that control the patterning of <i>Sox9</i>⁺/<i>Scx</i>⁺ superstructure progenitors in mouse and show that this program includes both global and regional regulatory modules. Using light-sheet fluorescence microscopy combined with genetic lineage labeling, we mapped the broad contribution of the <i>Sox9</i>⁺/<i>Scx</i>⁺ progenitors to the formation of bone superstructures. Then, by combining literature-based evidence, comparative transcriptomic analysis and genetic mouse models, we id2019-01-01T00:00:00Z2019 Jul2026-04-30T03:49:50.211Z2021-02-20T10:14:18ZS-EPMC66793673122164010.1242/dev.167882