Effect of 3-acetylpyridine on tissue differentiation of the embryonic chick limb

Abstract

3-AcETYLPYRiDiNE (3-AP) and 6-aminonicotinamide have a teratogenic effect on the development of the chick limb but have no effect of coadministered with nicotinamide¹. This has led Caplan to the hypothesis that nicotinamide has a crucial role in the spatial organisation of muscle and cartilage in the developing limb, high levels of nicotinamide specifying muscle, and low levels cartilage; with even the possibility that a metabolic gradient related to the blood supply could provide the positional information specifying the pattern of muscle and cartilage^2–5. The evidence for this hypothesis is based both on in vivo and in vitro studies, the latter claiming to show that 3-AP enhances chondrogenesis and inhibits myogenesis in cultured limb mesenchyme cells. As regards the in vivo effects, it is suggested that the gross muscle hypoplasia observed might be accounted for in terms of 3-AP switching the differentiation of mesenchyme cells from a myogenic fate to a chondrogenic one. This seemed to us to be an unlikely explanation, since the chondrogenic and myogenic tissues are already physically separated at stages when 3-AP is still known to have an effect (as late as 13d of incubation). It seemed much more likely that 3-AP was affecting muscle growth rather than its differentiation. We therefore made a histological study of the effect of 3-AP, and found that it was a potent destroyer of the peripheral nerves, and that there is no evidence to support the view that it affects mesenchyme differentiation.