My laboratory studies how specific synaptic connections are established by primary sensory neurons in the spinal cord. Sensory neurons supplying muscle versus skin make very different synaptic connections within the spinal cord. we have shown that molecular signals within developing limbs specify these central patterns of connections.

A search for these molecular signals has identified LMO4, a protein that regulates LIM homeodomain transcription factors, as a signal that is differentially expressed in sensory neurons supplying different muscles. Currently, we are changing the expression of LMO4 in developing embryos to determine the role of LMO4 in specifying the synaptic connections sensory neurons make within the spinal cord.

The laboratory also uses knock-out mice to examine the role of identified proteins in regulating synaptic specificity between spinal neurons. Individual members of the ETS family of transcription factors are expressed in sensory and motor neurons innervating the same muscle, and deletion of one of these genes disrupts the synaptic connections between these neurons. Another transcription factor, Egr3, is required for the formation of muscle spindles, so by deleting this gene, one can test if the formation of specific sensory-motor synapses depends on the presence of appropriate peripheral targets. To test the effects of these genes on synaptic specificity, microelectrode recordings are made from motor neurons in an isolated preparation of the mouse spinal cord to measure the synaptic input these neurons receive from identified muscle sensory neurons.