Our lab has recently shown that BMP7 is necessary for the initial projection pattern of commissural (C) axons in the developing spinal cord. A role for BMPs as axon guidance signals constitutes a novel function for this family of cytokines. The long-term goals of this research proposal is to define components of the signal transduction pathway responsible for the bone morphogenetic protein (BMP)-mediated chemorepulsion for the bone morphogenetic protein (BMP)-mediated chemorepulsion or dorsal spinal cord C axons. To define this signaling pathway, target proteins of BMP signaling in dorsal spinal cord will be characterized using phosphorylation and in vitro kinase assays. In vivo functional analysis of identified candidate proteins will be carried using two complementary misexpression systems: in ovo chick electroporation and transgenic mice with expression driven by C neuron specific promoters. The proposed experiments will further our understanding of the mechanisms that govern neuronal connectivity in the developing spinal cord. A general understanding of chemorepulsive mechanisms can be applied to spinal cord injury research, where expression of chemorepellent proteins may help to steer axons away from inappropriate targets. Elucidation of the intracellular targets activated by BMP- mediated chemorepulsion may help to shed light on the mechanisms at work in these differential actions of BMPs.
