NEUROTROPHIN-3 STIMULATES THE DIFFERENTIATION OF MOTONEURONS FROM AVIAN NEURAL-TUBE PROGENITOR CELLS

Neurotrophin 3 (NT-3) promotes differentiation of neural tube progenit ors into motoneurons expressing the BEN/SC1 and islet-1 epitopes. A 1. 75- to 6.7-fold increase in BEN-positive motoneurons was obtained when quail neural tube cells were cultured with NT-3 at 0.1-10 ng/ml, resp ectively. In contrast, the overall number of cells, as well as the pro portion of motoneurons that developed from cycling precursors, did not change. Addition of NT-3 at 1 ng/ml to cells obtained from ventral ha lf-neural tubes promoted a 2.5-fold stimulation in motoneuron number, confirming the specificity of the effect. Moreover, NT-3 had no signif icant effect on survival of differentiated avian motoneurons. The dist ribution of trkC mRNA, which encodes the high-affinity receptor for NT -3, is consistent with these findings. trkC expression is homogeneous in the embryonic day 2 (E2) neural tube, becomes restricted to the man tle layer on E3, where differentiation occurs, and disappears from the ventral third of the E4-E5 spinal cord right before the onset of norm al motoneuron death. These results suggest that NT-3 and trkC regulate early neurogenesis in the avian central nervous system.