Abstract
Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA lineage neurons. Accordingly, knockout of Runx1 leads to the selective loss of sensory innervation to the epidermis, whereas deep tissue innervation and two types of deep tissue pain are unaffected. Within these cutaneous neurons, Runx1 suppresses a large molecular program normally associated with sensory neurons that innervate deep tissues, such as muscle and visceral organs. Ectopic expression of Runx1 in these deep sensory neurons causes a loss of this molecular program and marked deficits in deep tissue pain. Thus, this study provides insight into a genetic program controlling the segregation of cutaneous versus deep tissue pain pathways.
Highlights
The dorsal root ganglia (DRGs) are composed of a heterogeneous population of primary sensory neurons, including nociceptors, mechanoreceptors, thermoceptors, and pruriceptors (Basbaum et al, 2009; Delmas et al, 2011; Marmigere and Ernfors, 2007)
The peripheral targets of DRG neurons can be divided into two main zones based on a radial topographical body plan: (1) superficial tissues, the largest being the epidermis of the skin and (2) deep tissues, including the dermis, muscle, bone, and visceral organs
The superficial tissues and the deep tissues stem from distinct germ layers, with the epidermis derived from the ectoderm, and the deep tissues derived from the mesoderm and endoderm (Gilbert, 2000)
Summary
The dorsal root ganglia (DRGs) are composed of a heterogeneous population of primary sensory neurons, including nociceptors, mechanoreceptors, thermoceptors, and pruriceptors (Basbaum et al, 2009; Delmas et al, 2011; Marmigere and Ernfors, 2007). The peripheral targets of DRG neurons can be divided into two main zones based on a radial topographical body plan: (1) superficial tissues, the largest being the epidermis of the skin and (2) deep tissues, including the dermis, muscle, bone, and visceral organs. The rationale for this division is twofold. The dearth of information on deep tissue pain-related sensory neurons belies their clinical relevance, as most medical cases of pain relate to muscle, bone, and visceral pain, as opposed to cutaneous pain (Ness and Gebhart, 1990)
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