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Publication : The emergence of transcriptional identity in somatosensory neurons.

First Author  Sharma N Year  2020
Journal  Nature Volume  577
Issue  7790 Pages  392-398
PubMed ID  31915380 Mgi Jnum  J:292971
Mgi Id  MGI:6445998 Doi  10.1038/s41586-019-1900-1
Citation  Sharma N, et al. (2020) The emergence of transcriptional identity in somatosensory neurons. Nature 577(7790):392-398
abstractText  More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments(1-4). It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process; disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors.
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