Region Specific Central Arbor Morphologies of Nociceptive Afferents Develop Independently of Their Peripheral Target Innervation

ABSTRACT Functionally important regions of sensory maps are overrepresented in the sensory pathways and cortex, but the underlying developmental mechanisms are not clear. In the spinal cord dorsal horn (DH), we recently showed that paw innervating Mrgprd+ non-peptidergic nociceptors display distinctive central arbor morphologies that well correlate with increased synapse transmission efficiency and heightened sensitivity of distal limb skin. Given that peripheral and central arbor formation of Mrgprd+ neurons co-occurs around the time of birth, we tested whether peripheral cues from different skin areas and/or postnatal reorganization mechanisms could instruct this somatotopic difference among central arbors. We found that, while terminal outgrowth/refinement occurs during early postnatal development in both the skin and the DH, postnatal refinement of central terminals precedes that of peripheral terminals. Further, we used single-cell ablation of Ret to genetically disrupt epidermal innervation of Mrgprd+ neurons and revealed that the somatotopic difference among their central arbors was unaffected by this manipulation. Finally, we saw that region-specific Mrgprd+ central terminal arbors are present from the earliest postnatal stages, before skin terminals are evident. Together, our data indicate that region-specific organization of Mrgprd+ neuron central arbors develops independently of peripheral target innervation and is present shortly after initial central terminal formation, suggesting that either cell-intrinsic and/or DH local signaling may establish this somatotopic difference.