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 b oth mouse and human, and that MSX2 dosage is critical to normal osteogenesi s. Another study, also in this issue, indicates that a loss-of-function mut ation in MSX1 results in human cleft palate(3). Msx genes interact with oth er genes (for example, the gene encoding TGF beta 3) to specify normal or c left palate development, raising the possibilities of both prenatal diagnos is and therapeutic treatment of human cleft palate. The dose sensitivity an d interaction of craniofacial genes may be the basis for generating the imp ortant subtle Variations in human faces.