title: Dicer maintains the identity and function of proprioceptive sensory neurons.
abstract: Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N.Neuron80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O.Nat Neurosci17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T.Mol Neurobiol44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive 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. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons.NEW & NOTEWORTHYWe have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, microRNAs are crucially important for maintaining proprioception. Additionally, this study hints at the larger question of how neurons maintain their functional and molecular specificity.
authors.affiliation: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Sean M
authors.initials: SM
authors.lastname: O'Toole
authors.affiliation: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Ferrer
authors.affiliation: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mekonnen
authors.affiliation: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Haihan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shima
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Wright State University, Dayton, Ohio.
authors.forename: David R
authors.initials: DR
authors.lastname: Ladle
authors.affiliation: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts; and nelson@brandeis.edu.
authors.forename: Sacha B
authors.initials: SB
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology*; D016923:Cell Death; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009470:Muscle Spindles / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology; D010320:Parvalbumins / Q000378:metabolism; D011434:Proprioception; D011499:Protein Processing, Post-Translational; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D010320:Parvalbumins; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Dicer; cell identity; proprioceptor