Comprehensive mapping of sensory and sympathetic innervation of the developing kidney

The kidneys act as finely tuned sensors to maintain physiological homeostasis. Both sympathetic and sensory nerves modulate kidney function through precise neural control. However, how the kidneys are innervated during development to support function remains elusive. Using light-sheet and confocal microscopy, we generated anatomical maps of kidney innervation across development. Kidney innervation commences on embryonic day 13.5 (E13.5) as network growth aligns with arterial differentiation. Fibers are synapsin I⁺, highlighting ongoing axonogenesis and potential signaling crosstalk. By E17.5, axons associate with nephrons, and the network continues to expand postnatally. CGRP⁺, substance P⁺, TRPV1⁺, and PIEZO2⁺ sensory fibers and TH⁺ sympathetic fibers innervate the developing kidney. TH⁺ and PIEZO2⁺ axons similarly innervate the human kidney, following the arterial tree to reach targets. Retrograde tracing revealed the primary dorsal root ganglia, T10-L2, from which sensory neurons project to the kidneys. Together, our findings elucidate the temporality and neuronal diversity of kidney innervation.