APOPTOSIS IN XENOPUS TADPOLE TAIL MUSCLES INVOLVES BAX-DEPENDENT PATHWAYS

Apoptosis is a fundamental mechanism implicated in normal development, One of the most spectacular developmental events involving apoptosis is tail regression during amphibian metamorphosis. We analyzed how thy roid hormone (3, 5, 3'-triiodothyronine, T-3), the orchestrator of met amorphosis, affects expression and function of the proapoptotic gene B ax in the tail muscle of free-living Xenopus tadpoles, During natural metamorphosis Bax mRNA was expressed in tail muscles and was spatially correlated with apoptosis, Precocious treatment of tadpoles with T-3 induced Bar expression and apoptosis. To verify that Bar expression wa s causally related to apoptosis we used a naked DNA gene transfer meth od to express Bar in the dorsal tail muscle, This induced apoptosis, a nd the process was exacerbated by T-3 treatment. To determine whether T-3 effects on Bar expression involved transcriptional regulation, we injected a Bar promoter sequence into dorsal and caudal tail muscles. In the dorsal muscle, T-3 treatment did not affect transcription from tile Bar promoter, However, in the caudal muscle, T-3 treatment signif icantly increased Bar transcription, We conclude that T-3-induced apop tosis in Xenopus tadpole tail muscles involves Bar-activating and Bar- synergistic mechanisms, These programs are induced in spatially and te mporally distinct manners.