Temporal Analysis of Sensory Neuron Diversification

The vertebrate somatosensory system consists of a multitude of neurons transducing an array of environmental stimuli, ranging from proprioceptive neurons that detect muscle stretch to thermoreceptive neurons that detect temperature. Such a diverse population is required to accurately interpret environmental cues so that the organism can appropriately respond to rewarding or dangerous stimuli. Interestingly, diverse neurons that transduce modality-specific stimuli originate from similar neural progenitor populations, but quickly acquire unique protein expression profiles and mature through temporally independent paths. Naturally occurring cell death and axon degeneration during development permits progressive refinement of sensory circuits. In Chapter II, we interrogated how/if neuronal subtypes differentially die, and we investigated whether the neurotrophin receptor p75NTR is required for developmental cell death across neuronal subtypes. We find that neurons derived from the earlier progenitor population (TrkB+, TrkC+, and eRet neurons) complete developmental cell death prior to neurons derived from the later progenitor population (TrkA+ neurons) (Cheng et al., 2018). We also find that p75NTR restricts the magnitude but not temporal window of death for each subpopulation (Cheng et al., 2018). Within Chapter III, we utilized single cell mass cytometry, CyTOF, to create a high-dimensional developmental map of all DRG cells throughout embryonic and early postnatal development. This next generation single cell analysis recapitulates observations made via classic approaches (i.e. immunohistochemistry). Furthermore, graphical representation of the change in this high dimensional data set (FLOW-MAP) recapitulate lineage progression consistent with previous experiments, where TrkB+ and/or TrkC+ sensory neuron mature prior to TrkA+ sensory neuron populations. This foundational work provides the basis for future studies investigating how candidate proteins influence population dynamics. Collectively, these findings provide a conceptualization of how populations as diverse as sensory neurons with unique temporal and expression characteristics mature throughout development. Additional studies building upon these findings will elucidate how critical and multifunctional proteins, such as neurotrophins, differentially mediate development.