Dicer maintains the identity and function of proprioceptive sensory neurons

During development neurons achieve a high degree of specialization (Fishell and Heintz, 2013). Over time, while continuously recycling their components and despite transcriptional noise, their own respective properties remain intact. The transcription factors that play a large role in initially establishing neuronal identity can be required for maintaining it (Deneris and Hobert, 2014). Post-transcriptional regulation is also important to differentiation (Bian and Sun, 2011) but its role in maintaining cell identity is less established. To better understand how post-transcriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory class, whose properties are well established and display clear differences when compared to other neurons in the ganglion. By conditionally ablating Dicer in mice, using a parvalbumin (Pvalb) driven cre, we impaired post-transcriptional regulation in the proprioceptive sensory neuron population. KO animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is mirrored by a cell-death within the DRG. Before cell-loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of non-proprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Post-transcriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. mRNA levels were examined in the lumbar 4 dorsal root ganglion parvalbumin positive neurons with and without conditional ablation of dicer driven by parvalbumin-cre.