Scaling proprioceptor gene transcription by retrograde NT3 signaling

The assembly of neuronal circuits depends critically on the sequential activation of transcriptional programs in defined neuronal sub-populations. In the spinal cord, retrograde signaling interactions from the periphery have been shown to be essential for the onset of these programs and the establishment of specific sensory-motor connectivity (Wenner and Frank, J Neurosci 15(12) 1995; Lin et al., Cell 95(3) 1998). Target-induced transcriptional programs of the ETS transcription factor family control several important aspects of late motor circuit assembly in the spinal cord, both in spinal motor neurons as well as in proprioceptive sensory neurons, two neuronal subpopulations connected in the spinal monosynaptic reflex circuit (Arber et al., Cell 101(5) 2000; Livet et al., Neuron 35(5) 2002; Patel et al., Neuron 38(3) 2003; Vrieseling and Arber, Cell 127(7) 2006).
This study was aimed at a genome-wide analysis of target-induced gene cascades in proprioceptive afferents with the goal of defining in an unbiased way the pathways linking target-derived factors to central motor circuit assembly. We used gene expression profiling of purified proprioceptive afferents in combination with Affymetrix chip technology to study genes regulated by peripheral neurotrophin 3 (NT3). Data mining of our results demonstrates that several parallel signaling pathways influence differentiation of proprioceptive afferents retrogradely. These findings therefore suggest that NT3 does not solely induce the transcriptional program orchestrated by the ETS transcription factor Er81 in proprioceptive afferents, but also triggers additional pathways which may influence connectivity of motor circuits in the spinal cord retrogradely.