Abstract Dr. R. Murray
Title of Project The Role of Bone Morphogenetic Proteins in Nociceptive Neuron Development
Abstract In the mammalian nervous system, pain is sensed by nociceptive neurons that reside in the dorsal root ganglia (DRG) that flank the spinal cord. These neurons derive from migrating neural crest cells and are absent in mice deficient in neurogenin1, NGF, or trkA, indicating that these genes are required for the generation, differentiation, or survival of these medically important neurons. However, we know little about the factors that regulate the generation of the proper number of nociceptive neurons during development or about the formation of proper connectivity with target tissues. The development of many types of neurons is regulated by members of the bone morphogenetic protein (BMP) growth factor family, and BMP ligands, as well as type I and type II BMP receptors, are expressed in developing DRGs. Cell culture experiments show that BMPs promote the expression of a neuropeptide known to be expressed by nociceptive neurons. To examine the role of BMPs in nociceptive neuron development and to test the hypothesis that endogenously expressed BMPs regulate the differentiation of nociceptive neurons, the following specific aims will be pursued: 1) the spatial and temporal expression pattern of BMP ligands and receptors during DRG development will be determined; 2) promoter elements from the neurogenin1 gene will be examined for the ability to drive the expression of a reporter gene in vivo; and 3) the role of BMPs in nociceptive neuron development will be tested by upregulating and downregulating BMP signaling in developing nociceptive neurons in vivo. Determining the role of BMPs in the development of nociceptive neurons will contribute to our understanding of the molecular regulation of growth and differentiation in the developing mammalian nervous system. This information should provide insights into strategies for replacing cells lost to disease or injury, and potentially for alleviating chronic pain.
Updated 10/31/2005
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