THE SURVIVAL OF NGF-DEPENDENT BUT NOT BDNF-DEPENDENT CRANIAL SENSORY NEURONS IS PROMOTED BY SEVERAL DIFFERENT NEUROTROPHINS EARLY IN THEIR DEVELOPMENT

Recent work has shown that the survival of the nerve growth factor (NG F)-dependent trigeminal ganglion neurons of the mouse embryo is promot ed by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT- 3) during the early stages of target field innervation (Buchman and Da vies, (1993) Development, 118, 989-1001). The present study was undert aken to ascertain if responsiveness to multiple neurotrophins is a uni versal feature of the early stages of neuronal development or is restr icted to only certain kinds of neurons. To address this issue, we took advantage of the accessibility, from an early developmental stage, of several populations of cranial sensory neurons in the chicken embryo that depend for survival on just one or two known neurotrophins during the phase of naturally occurring cell death. During the mid-embryonic period (E10 to E12) when the number of sensory neurons is declining d ue to naturally occurring neuronal death, the neurons of the jugular g anglion and the dorsomedial part of the trigeminal ganglion (DMTG) wer e supported by NGF, the neurons of the ventrolateral part of the trige minal ganglion (VLTG) were supported by BDNF and the nodose ganglion c ontained a major subset of neurons supported by BDNF and a minor subse t supported by NT3. Earlier in development (E6), the survival of DMTG and jugular neurons was additionally promoted by BDNF and NT-3. Zn con trast, E6 VLTG neurons did not exhibit a survival response to either N GF or NT-3, and E6 nodose neurons did not exhibit a survival response to NGF. The loss of the early survival response of DMTG and jugular ne urons to BDNF and NT-3 was due to a marked shift in the dose-response to these neurotrophins (by more than four orders of magnitude between E6 and E8). These findings indicate that the responsiveness of certain populations of neurons to neurotrophins becomes restricted during dev elopment and raise the possibility that neuron-target interactions inv olving multiple neurotrophins regulate neuronal survival in vivo.