Development of Sensory Neurons in the Absence of NGF/TrkA Signaling In Vivo

• Published in: Neuron (Cambridge, Mass.) Mass.), 2000-02, Vol.25 (2), p.345-357
• Main Authors: Patel, Tushar D, Jackman, Alana, Rice, Frank L, Kucera, Jan, Snider, William D
• Format: Article
• Language: English
• Subjects: Animals; bcl-2-Associated X Protein; Calcitonin Gene-Related Peptide - genetics; Cell Count; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured; Female; Ganglia, Spinal - cytology; Ganglia, Spinal - embryology; Gene Expression Regulation, Developmental; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nerve Growth Factor - pharmacology; Neurons, Afferent - chemistry; Neurons, Afferent - cytology; Neurons, Afferent - physiology; Phenotype; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Receptor, trkA - genetics; Signal Transduction - physiology; Skin - innervation; Spinal Cord - cytology; Substance P - genetics
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80899-5

The neurotrophin survival dependence of peripheral neurons in vitro is regulated by the proapoptotic BCL-2 homolog BAX. To study peripheral neuron development in the absence of neurotrophin signaling, we have generated mice that 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. These neurons extend axons through the dorsal roots and collateral branches into the dorsal horn. In contrast, superficial cutaneous innervation is absent. Furthermore, rescued sensory neurons fail to express biochemical markers characteristic of the nociceptive phenotype. These findings establish that NGF/TrkA signaling regulates peripheral target field innervation and is required for the full phenotypic differentiation of sensory neurons.