The retinoic acid-indcible transcription factor AP-2 isexpressed in epithlial and neural crest cell linegages during murine development1-5. AP-2 can regulate neural and epithelial gene transcriptio, and is associated with overexpression of c-erbB-2 in human breast-cancer cel lines4-6. To ascertain the importance of AP-2 in human breast-cancer cell lines4-6. To ascertain the importance of AP-2 for normal development, we have derived mice containing a homozygous disruption of the AP-2 gene. These AP-2-ull mice have multpie congenitL development, w have derived mice containing a homzygous disruption of the AP-2 gene. These AP-2 null mice have multiple congenital defect and die at birth. In particuar the AP-2 knockout mice exhibit anencephay, craniorfacia defects and thoraco-abdominoschisis. Skeletal defects occur in the head and trunk region, where many bones are deformed ofabsent. Analysis of tese mice earlier in embryogenesis indicates a failure of cranial neural-ture closure and defect in cranial ganglia development. We have shown that Ap-2 is fundamental regulator of manmmalian craniofacia development.