Similarly, homozygous loss-of-function mutations in CYP26B1, one of the major RA-metabolizing enzymes, cause advanced bone age, premature epiphyseal fusion, and craniosynostosis.
Analyses of murine embryos exposed to a chemical inhibitor of Cyp26 enzymes and zebrafish lines with mutations in cyp26b1 suggest that the endochondral bone fusions are due to unrestricted chondrogenesis at the presumptive sites of joint formation within cartilaginous templates, whereas craniosynostosis is induced by a defect in osteoblastic differentiation.