Conspicuously, ENU-induced Nell-1-deficient mice, while exhibiting similar CCD-like calvarial phenotypes as Runx2+/− mice, also display rib cage vertebral abnormalities not described in Runx2+/− mice.(16) This, coupled with our current data demonstrating Nell-1 induction of Alp and Opn expression in Runx2−/− NMCCs, indicates that a subset of Nell-1 effects is not necessarily related to Runx2 modulation. This evidence concerns the gene RUNX2 and cleidocranial dysplasia 1.