IN-VITRO MODEL OF SYNDACTYLY REPLICATES THE MORPHOLOGIC FEATURES OBSERVED IN-VIVO

Syndactyly is a common congenital hand anomaly that may occur after ex posure to teratogens. We have developed an in vitro model of syndactyl y to investigate the molecular mechanisms underlying this malformation of digit development. Retinoic acid, which regulates pattern formatio n in vertebrate limb development and is associated with teratogenic ma lformations, was used in the development of this syndactyly model syst em. Pregnant Swiss-Webster mice were given retinoic acid by oral gavag e on days 10 and 11 of embryonic development (E10 and E11, respectivel y). The mice were sacrificed on gestational days 13 and 17 (E13, E17) and immediately postnatally (PN). The fetuses were removed and the for elimbs dissected under the operating microscope. The E13 limbs were cu ltured for 4 days (E13+4) in an organ culture system using a serumless , chemically defined medium. The E17, PN, and E13+4 forelimbs were cri tically examined for malformations of digit separation and digit devel opment. Retinoic acid-induced fetal mouse forelimb syndactyly was obse rved in all the groups; 81 percent of E17 limbs, 75 percent of PN limb s, and 77 percent of E13+4 limbs had syndactyly. The morphology of the digital malformations was similar in the E17, PN, and E13+4 limbs. Th is in vitro model permits further studies to characterize the molecula r changes that occur during the development of a congenital hand anoma ly.