Air-breathing behavior underlies the cell death in limbs of Rana pirica tadpoles.

Amphibians shape their limbs by differential outgrowth of digits and interdigital regions. In contrast, amniotes employ cell death, an additional developmental system, to determine the final shape of limbs. Previous work has shown that high oxygen availability is correlated with the induction of cell death in developing limbs. Given the diversity of life histories of amphibians, it is conceivable that some amphibians are exposed to a high-oxygen environment during the tadpole phase and exhibit cell death in their limbs. Here, we examined whether air-breathing behavior underlies the cell death in limbs of aquatic tadpoles of the frog species Rana pirica. Our experimental approach revealed that R. pirica tadpoles exhibit cell death in their limbs that is likely to be induced by oxidative stress associated with their frequent air-breathing behavior.