RUNX2 and cleidocranial dysplasia 1: Runx2-null mice exhibit a complete absence of bone formation.241 It is unequivocally required for embryonic ossification,207 postnatal skeletogenesis,242–244 and craniofacial patterning.245,246 Runx2 activity is tightly linked to BMP signaling; autocrine BMPs activate Runx2 expression,247 BMP2-induced osteogenesis strictly depends on Runx2,248 and Smad1 directly binds to the Runx2 promoter to regulate osteoblast-specific gene expression.249 Heterozygous mutations in RUNX2 cause cleidocranial dysplasia, an autosomal-dominant skeletal disorder.250