Scaling proprioceptor gene transcription by retrograde NT3 signaling

• Published in: PloS one 2012-09, Vol.7 (9), p.e45551
• Main Authors: Lee, Jun, Friese, Andreas, Mielich, Monika, Sigrist, Markus, Arber, Silvia
• Format: Article
• Language: English
• Subjects: Animals; Biology; Biomedical research; Cell Separation; Cell survival; Cellular signal transduction; Cluster Analysis; Combinatorial analysis; Developmental stages; Dorsal root ganglia; Experiments; Ganglia, Spinal - metabolism; Gene Deletion; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic aspects; Genomes; Genomics; Hybridization; Kinases; Male; Maturation; Mice; Mice, Transgenic; Muscle, Skeletal - metabolism; Mutation; Neurons; Neurotrophin 3; Neurotrophin 3 - genetics; Neurotrophin 3 - metabolism; Neurotrophins; Physical Exertion - genetics; Physiological aspects; Proprioceptors; Receptors, GABA-A - genetics; Rodents; Scaling; Sensory neurons; Sensory Receptor Cells - cytology; Sensory Receptor Cells - metabolism; Sensory receptors; Signal Transduction; Signaling; Spinal cord; Subpopulations; Survival; Transcription; Transcription, Genetic
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045551

Cell-type specific intrinsic programs instruct neuronal subpopulations before target-derived factors influence later neuronal maturation. Retrograde neurotrophin signaling controls neuronal survival and maturation of dorsal root ganglion (DRG) sensory neurons, but how these potent signaling pathways intersect with transcriptional programs established at earlier developmental stages remains poorly understood. Here we determine the consequences of genetic alternation of NT3 signaling on genome-wide transcription programs in proprioceptors, an important sensory neuron subpopulation involved in motor reflex behavior. We find that the expression of many proprioceptor-enriched genes is dramatically altered by genetic NT3 elimination, independent of survival-related activities. Combinatorial analysis of gene expression profiles with proprioceptors isolated from mice expressing surplus muscular NT3 identifies an anticorrelated gene set with transcriptional levels scaled in opposite directions. Voluntary running experiments in adult mice further demonstrate the maintenance of transcriptional adjustability of genes expressed by DRG neurons, pointing to life-long gene expression plasticity in sensory neurons.