Evidence that retinoic acid-induced apoptosis in the mouse limb bud core mesenchymal cells is gene-mediated.

The evidence presented here strengthens the argument that RA-induced truncation defects of the embryonic limb, and probably other teratogenic effects, are mediated by the nuclear retinoid receptors, particularly the RAR-beta 2 isoform. Although apoptotic cell death and an increased transglutaminase (tTG) activity accompany teratogenesis, it should be emphasized that the increased levels of RAR-beta 2 may influence additional events in limb development, e.g., modulation of connective tissue differentiation and an inhibition of chondrogenesis. Further work entails screening the effects of RA on genes targeted by the receptors.