Development of sensory neurons in the absence of NGF/TrkA signaling in vivo

The neurotrophin survival dependence of peripheral neurons in vitro is regu lated by the proapoptotic BCL-2 homolog BAX. To study peripheral neuron dev elopment in the absence of neurotrophin signaling, we have generated mice t hat are double null for BAX and nerve growth factor (NGF), and BAX and the NGF receptor TrkA. All dorsal root ganglion (DRG) neurons that normally die in the absence of NGF/TrkA signaling survive if BAX is also eliminated. Th ese neurons extend axons through the dorsal roots and collateral branches i nto the dorsal horn. In contrast, superficial cutaneous innervation is abse nt. Furthermore, rescued sensory neurons fail to express biochemical marker s characteristic of the nociceptive phenotype. These findings establish tha t NGF/TrkA signaling regulates peripheral target field innervation and is r equired for the full phenotypic differentiation of sensory neurons.