Hox genes and circuit assembly in the spinal cord

In addition to motor neurons, Hox protein expression localizes to the two other major classes of neurons in the spinal cord - sensory neurons and interneurons. A future goal of our lab will be to further explore whether Hox proteins contribute to specificity of connections between motor neurons, sensory neurons, and interneurons..

Do Hox proteins contribute to circuit assembly within the spinal cord?

One of the simplest circuits in the spinal cord is the monosynaptic stretch-reflex circuit; consisting of a motor neuron, a sensory neuron, and a muscle target. The specificity of connections in this circuit is thought to emerge in an activity-independent manner, making it an attractive system to explore the genetic basis of circuit assembly.

We have found that the expression of Hox factors in proprioceptive sensory neurons parallels the segment-specific Hox patterns in motor neurons, raising the possibility that Hox factors are involved in the formation of stretch-reflex circuits. A potential role for Hox factors in sensory-motor connectivity will be explored using gene-targeting strategies in mouse to generate motor and sensory neurons that lack or misexpress specific Hox proteins. A potential outcome of these studies is that altering Hox expression will lead to the failure of neurons to innervate their appropriate synaptic targets. This hypothesis will be tested using anatomical assays to trace the projections of sensory and motor axons, and to define the molecular properties of their monosynaptic connections.