Title: Proprioceptor subtype identity specified by limb-derived signals
Description: The provision of proprioceptive feedback from limb muscle to spinal motor neuron is essential for the generation of coordinated movement. Proprioceptive sensory neurons form a precise matrix of connections with motor neurons and do so in the absence of patterned activity, implying the existence of proprioceptor subtype identities that mediate selective connectivity. The developing limb has been shown to influence the pattern of connections made by proprioceptors with motor neurons, suggesting that the patterning cues distributed along its cardinal axes are capable of influencing the molecular identities of proprioceptors. In this thesis, I describe efforts to characterize the molecular diversity of proprioceptors supplying distinct muscles located at different dorsoventral and proximodistal positions within the mouse hindlimb. I demonstrate the selective expression of several genes – cdh13, vstm2b, sema5a, and crtac1 – by proprioceptors supplying defined positional domains of the limb.

I proceed to determine the limb tissue source of proprioceptor patterning information by examining the expression of these genes in mice in which one of three tissues encountered by proprioceptors – the motor axon, limb mesenchyme, and target muscle – has been genetically manipulated, revealing that both mesenchyme and muscle supply cues capable of directing proprioceptor gene expression. Finally, I show that one marker of proprioceptor muscle-type identity, cdh13, mediates the formation of selective connections between proprioceptors and motor neurons, thereby establishing a molecular link between proprioceptor subtype identity and patterned central connectivity.