Correlation between RA-induced apoptosis and patterning defects in regenerating fins and limbs.

We have compared the ability of RA to induce apoptosis in regenerating fins and limbs in order to establish whether there may be a possible causal relationship between RA-induced cell death and the different patterning abnormalities observed in these two systems following RA treatment. In regenerating fins RA affects the anteroposterior axis and induces narrowing of the fin and fusion of rays. In regenerating limbs however, it mainly affects the proximodistal axis, where dose-dependent duplications of segments are observed. We report here that RA increases cell death by apoptosis both in fin and limb regenerates independently from the route of administration, but in distinct cell populations. In regenerating fins, RA-induced apoptosis is observed only in the wound epidermis, whereas in regenerating limbs significant apoptosis is observed mainly in the blastema mesenchyme. Altogether, these findings support the view that RA-induced apoptosis is causally related to the patterning defects observed in fins and limbs.