Induction of skeletal malformations in organ cultures of mammalian embryonic tissues

Summary

Abnormalities of the cartilaginous limb bone anlagen resembling “syndactyly” and “phocomelia” can be mimicked entirely in vitro, using an organ culture system which allows the differentiation of mouse limb buds from the blastema stage (day 11.0 of gestation) to well recognizable cartilaginous anlagen of the long bones and the hand (or foot) skeleton (metacarpal anlagen) within 6 to 7 days. As reported here such “malformations” as triggered in vitro by 6-mercaptopurine (6-MP) should be distinguished from less specific effects, such as failure of the explant to develop typically in a proximodistal direction and to grow or form cartilage, which are produced by a variety of drugs or by altering the medium composition or other culture conditions. When culturing limb buds from embryos exposed in utero to 5-bromodeoxyuridine (BUdr) in a normal medium it was possible to obtain polydactyly in about 30% of the explants. The test system used provides another way of elucidating the mode of action of teratogenic agents, and of mechanisms involved in an abnormal mammalian development.