Etv1 inactivation reveals proprioceptor subclasses that reflect the level of NT3 expression in muscle targets

The organization of spinal reflex circuits relies on the specification of distinct classes of proprioceptive sensory neurons (pSN), but the factors that drive such diversity remain unclear. We report here that pSNs supplying distinct skeletal muscles differ in their dependence on the ETS transcription factor Etv1 for their survival and differentiation. The status of Etv1-dependence is linked to the location of proprioceptor muscle targets: pSNs innervating hypaxial and axial muscles depend critically on Etv1 for survival, whereas those innervating certain limb muscles are resistant to Etv1 inactivation. The level of NT3 expression in individual muscles correlates with Etv1-dependence and the loss of pSNs triggered by Etv1 inactivation can be prevented by elevating the level of muscle-derived NT3-revealing a TrkC-activated Etv1-bypass pathway. Our findings support a model in which the specification of aspects of pSN subtype character is controlled by variation in the level of muscle NT3 expression and signaling.