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Temporally restricted death and the role of p75NTR as a survival receptor in the developing sensory nervous system
Authors:Irene Cheng  Lucy Jin  Lucy C Rose  Christopher D Deppmann
Institution:1. Department of Biology, University of Virginia, Charlottesville, Virginia;2. Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia;3. Department of Cell Biology, University of Virginia, Charlottesville, Virginia;4. Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia
Abstract:The peripheral somatosensory system overproduces neurons early in development followed by a period of cell death during final target innervation. The decision to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is mediated by target‐derived neurotrophic factors and their cognate receptors. Subsets of peripheral somatosensory neurons can be crudely defined by the neurotrophic receptors that they express: peptidergic nociceptors (TrkA+), nonpeptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and proprioceptors (TrkC+). A direct comparison of early developmental timing between these subsets has not been performed. Here we characterized the accumulation and death of TrkA, B, C, and Ret+ neurons in the DRG as a function of developmental time. We find that TrkB, TrkC, and Ret‐expressing neurons in the DRG complete developmental cell death prior to TrkA‐expressing neurons. Given the broadly defined roles of the neurotrophin receptor p75NTR in augmenting neurotrophic signaling in sensory neurons, we investigated its role in supporting the survival of these distinct subpopulations. We find that TrkA+, TrkB+, and TrkC+ sensory neuron subpopulations require p75NTR for survival, but proliferating progenitors do not. These data demonstrate how diverging sensory neurons undergo successive waves of cell death and how p75NTR represses the magnitude, but not developmental window of this culling. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 701–717, 2018
Keywords:neurotrophic factor  sensory  development  apoptosis  p75NTR  dorsal root ganglion  peripheral nervous system
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