Abstract
Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.
Highlights
Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli
It is essential to dissect and understand the precise temporal progression of the gene-regulatory networks that produce and assemble neuronal complexity. Such complexity is found in all parts of the developing nervous system, including the highly heterogeneous population of sensory neurons—cells that live in dorsal root ganglia (DRG) and provide us with sensations of touch, pain, itch, temperature and position in space[5]
We FACS isolated tdTomato positive (TOM+) cells isolated from mouse lines which selectively represent all neural crest cells (NCCs) (Wnt1Cre;R26tdTOM and Plp1CreERT2;R26tdTOM) and from neuron-specific Cre mouse lines (Isl1Cre;R26tdTOM and Ntrk3Cre; R26tdTOM) to obtain an enrichment of somatosensory neuronal populations (Supplementary Fig. 1a, b) from E9.5, E10.5, E11.5 and E12.5 and sequenced mRNAs of single cells with high coverage using Smart-seq[2] protocol (Fig. 1a and Supplementary Fig. 1c, d; see “Methods”)
Summary
Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. It is essential to dissect and understand the precise temporal progression of the gene-regulatory networks that produce and assemble neuronal complexity Such complexity is found in all parts of the developing nervous system, including the highly heterogeneous population of sensory neurons—cells that live in dorsal root ganglia (DRG) and provide us with sensations of touch, pain, itch, temperature and position in space[5]. Mechanoreceptors express RET and MAFA and/or TRKB, proprioceptors express tropomyosin receptor kinase C (TRKC) and RUNX3, and the small Aδ-nociceptor population expresses TRKA Later, these populations will diversify even further, giving rise to additional subtypes representing the medium-to-large diameter DRG neurons responsible for muscle proprioceptive feedback and skin mechanosensation modalities[5]. Our data provide insights into the structure of the Waddingtonian landscape of the sensory lineage and suggest that counteracting gene-regulatory networks operate within immature postmitotic neurons, resulting in the emergence of alternative-lineage transcriptional programs defining the neuron fate choice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
