TrkB expression and early sensory neuron survival are independent of endogenous BDNF

Sensory neurons initially survive independently of neurotrophins in culture during the stage of development when their axons are growing to their targ ets. Because mRNAs encoding brain-derived neurotrophic factor (BDNF) and it s receptor tyrosine kinase TrkB are detectable in subsets of sensory neuron s from the earliest stages of their development, we investigated whether a BDNF autocrine loop is responsible for sustaining the survival of these neu rons during this early stage in their development. Low-density dissociated cultures of nodose and dorsal root ganglion neurons were established from w ild type and BDNF (-/-) mouse embryos at this stage and were grown in defin ed medium without added neurotrophins. Wild type and BDNF-deficient neurons survived equally well under these conditions, indicating that a BDNF autoc rine loop does not play a role in sustaining the survival of sensory neuron s during the earliest stages of their development. As sensory axons approac h their targets, TrkB expression increases in a subset of neurons that beco mes dependent on BDNF produced by other cells. Because numerous studies hav e shown that neurotrophins, including BDNF, increase expression of their re ceptors, we investigated whether endogenous BDNF is required for the increa se in TrkB expression observed during stage of development. Quantitative re verse transcriptase-polymerase chain reaction (RT-PCR) showed that the deve lopmental increase in TrkB mRNA expression occurred normally in the sensory ganglia of BDNF (-/-) embryos. Taken together, our studies of sensory neur on development in BDNF-deficient embryos have demonstrated that endogenous BDNF is neither required for the early survival of these neurons nor for th e induction of TrkB expression. (C) 2000 Wiley-Liss,Inc.