A hole in the head

Two studies in this issue^1,2 indicate that loss-of-function mutations in the MSX2 homeobox gene result in failure of cranial fontanelle closure in both mouse and human, and that MSX2 dosage is critical to normal osteogenesis. Another study, also in this issue, indicates that a loss-of-function mutation in MSX1 results in human cleft palate³. Msx genes interact with other genes (for example, the gene encoding TGFβ3) to specify normal or cleft palate development, raising the possibilities of both prenatal diagnosis and therapeutic treatment of human cleft palate. The dose sensitivity and interaction of craniofacial genes may be the basis for generating the important subtle variations in human faces.