Teneurin-3 and latrophilin-2 are required for somatotopic map development and somatosensory topognosis

Somatotopy is a recurring organizational feature of the somatosensory system where adjacent neurons and their connections represent adjacent regions of the body. The molecular mechanisms governing the formation of such "body maps" remain largely unknown. Here, we demonstrate that the cell surface proteins teneurin-3 and latrophilin-2 are expressed in opposing gradients aligning with the somatotopic map in the dorsal horn of the mouse spinal cord. Genetic manipulation of these proteins in the spinal dorsal horn or sensory neurons distorts the somatotopy of neuronal connections and impairs the accurate localization of a noxious stimulus on the surface of the body. Our work provides the foundation for a molecular model of somatotopic map formation and insights into the role of somatotopic maps in the ability to accurately locate somatosensory stimuli, also known as topognosis.