Regulation of neurotrophin receptor expression by retinoic acid in mouse sympathetic neuroblasts

We have studied the effect of retinoic acid on the expression of the neurot rophin receptors trkA, trkC, and p75 by neuroblasts and neurons at differen t axial levels along the embryonic mouse paravertebral sympathetic chain. I n dissociated cultures of sympathetic neuroblasts, retinoic acid inhibited the developmental increase in trkA mRNA expression and the developmental de crease in trkC mRNA expression that normally occurs in these cells but did not affect p75 mRNA expression. At higher concentrations, retinoic acid als o increased the proliferation of sympathetic neuroblasts. After sympathetic neuroblasts became postmitotic, retinoic acid no longer affected receptor expression. Studies with retinoic acid receptor agonists and antagonists in dicated that the effects of retinoic acid on neurotrophin receptor expressi on were mediated mainly by alpha retinoic acid receptors, not beta or gamma receptors. The observation that at-antagonists increased trkA mRNA express ion in intact sympathetic ganglion explants suggests that endogenous retino ic acid is a physiological regulator of trkA receptor expression.