Osteoblasts are derived from two distinct embryonic lineages: cranial
neural crest, and mesoderm. Both populations of cells are capable of forming
bone and cartilage during fetal development and during adult bone repair, but
whether they use equivalent molecular pathways to achieve osteoblast
differentiation is unknown. We addressed this question in the context of
cranial repair and focused on the role of Wnt signaling in mandibular skeletal
healing. Transgenic Wnt reporter mice were used to pinpoint Wnt-responsive
cells in the injury callus, and in situ hybridization was used to identify
some of the Wnt ligands expressed by cells during the repair process. A gene
transfer technique was employed to abrogate Wnt signaling during mandibular
healing, and we found that reparative intramembranous ossification requires a
functional Wnt pathway. Finally, we evaluated how constitutive activation of
the Wnt pathway, caused by mutation of the LRP5 receptor, affected bone repair
in the mandible. Taken together, these data underscore the functional
requirement for Wnt signaling in cranial skeletal healing.