Sensory neurons are a major derivative of the neural crest for which there have been no definitive molecular markers in mammals. We have developed a method that combines differential hybridization with degenerate RT-PCR to rapidly screen gene families for members exhibiting differential expression among tissues or cell types. We used this approach to search for transcription factor-encoding genes specifically expressed in mammalian sensory neurons. A novel paired homeodomain protein, called DRG11, was identified. DRG11 is expressed in most sensory neurons, including trkA-expressing neurons, but not in glia or sympathetic neurons. Unexpectedly, it is also expressed in the dorsal horn of the spinal cord, a region to which NGF-dependent sensory neurons project. These data suggest that DRG11 is not only a useful marker for sensory neurons, but may also function in the establishment or maintenance of connectivity between some of these neurons and their central nervous system targets.