An anatomical framework for cutaneous sympathetic organization in mice reveals overlapping ganglionic territories and long-range stellate projections

The sympathetic nervous system regulates skin homeostasis by controlling thermoregulation, piloerection, vascular tone, epithelial stem cell activity, and immune surveillance. Although sympathetic nerves remodel during aging and inflammatory skin disease, the anatomical organization of cutaneous sympathetic circuits remains poorly defined. Here, we established a skin-specific retrograde viral tracing approach to define the anatomical organization of cutaneous sympathetic innervation. Dual-color retrograde tracing revealed that cutaneous sympathetic innervation is strictly ipsilateral and organized into broad, overlapping territories rather than discrete segmental domains. Anterior dorsal skin received input from multiple thoracic ganglia, whereas posterior dorsal skin exhibited greater inter-animal variability. Unexpectedly, the stellate ganglion consistently contributed to anterior dorsal skin innervation and, in a substantial subset of mice, also innervated posterior dorsal skin despite the absence of continuous labeling of intervening thoracic ganglia. Dual-tracer experiments demonstrated that individual stellate ganglion neurons can innervate both anterior and posterior dorsal skin, revealing unexpectedly long-range cutaneous projections. These findings establish an anatomical framework for cutaneous sympathetic organization, reveal overlapping ganglionic territories, and identify the stellate ganglion as a previously unrecognized source of sympathetic input to anterior and posterior dorsal skin, providing a foundation for investigating sympathetic remodeling during aging and skin disease.