Proprioceptive sensory-driven mechanisms shape Clarke's column development.

Abstract

Coordinated locomotion depends not only on motor programs but also on the sensory feedback that refines them. Proprioceptive sensory neurons (pSNs) modulate motor circuits through direct synapses, yet their role in shaping spinal cord circuits has remained unclear. Here, we uncover an essential function for pSNs in organizing Clarke's column (CC) neurons, a major spinocerebellar population. Although CC neurons are born early in embryogenesis, their distinctive columnar architecture emerges postnatally and depends on direct pSN input. Genetic ablation of pSNs reduces the number of CC neurons and disrupts their somatic and dendritic organization. Blocking neurotransmission or eliminating Piezo2-dependent mechanotransduction produces overlapping defects, revealing that both the presence and activity of pSNs are required for CC maturation. RNA sequencing identifies a molecular signature of pSN-dependent regulation, implicating the axon guidance receptor Unc5c as a candidate regulator. Our findings reveal an unrecognized role for pSNs in spinal circuit development.