DIFFERENT NEUROTROPHINS ARE EXPRESSED AND ACT IN A DEVELOPMENTAL SEQUENCE TO PROMOTE THE SURVIVAL OF EMBRYONIC SENSORY NEURONS

To investigate if different neurotrophins regulate the survival of neu rons at successive developmental stages, we studied the effect of nerv e growth factor (NGF), brain-derived neurotrophic factor (BDNF) and ne urotrophin-3 (NT-3) on the survival of mouse trigeminal neurons at clo sely staged intervals in development. We show that during the earliest stages of target field innervation trigeminal neurons display a trans itory survival response to BDNF and NT-3. This response is lost as the neurons become NGF-dependent shortly before neuronal death begins in the trigeminal ganglion. BDNF and NT-3 mRNAs are expressed in the peri pheral trigeminal target field before the arrival of the earliest axon s and the onset of NGF mRNA expression. The levels of BDNF and NT-3 mR NAs peak during the early stages of target field innervation and decli ne shortly after the loss of neuronal responsiveness to BDNF and NT-3. Our study provides the first clear evidence that different target-der ived neurotrophins can act sequentially to promote the survival of dev eloping neurons.