Information processing in the nervous system relies on the separation of dendrites and axons. However, little is known about how dendrites and axons develop into distinct compartments. The long-term goal of this application is to define how neuronal compartmentalization is achieved during the development of neural circuits and how defects in that process lead to neurological and psychiatric diseases. The objective of this application is to delineate the signaling pathways that separate dendrite and axon development. Recent genetic studies on Drosophila have demonstrated that the fibroblast growth factor (FGF) receptors differentially control dendrite and axon development. The central hypothesis of this application is that the FGF receptors activate distinct signaling pathways to differentially control dendrite and axon development. We will test this hypothesis by pursuing three specific aims: 1) ) Identify the signaling pathway through which FGF receptors control dendrite-specific development;2) Determine whether FGF receptors regulate axon development through pathways different from dendrite development;3) Determine whether the roles of FGF receptors in the differential development of dendrites and axons are conserved in mammalian neurons. The approach is innovative because it takes advantage of genetic analysis to investigate the developmental differences between dendrites and axons in vivo and combines both Drosophila and mammalian systems to study evolutionarily conserved mechanisms. The proposed research is significant because it is expected to advance knowledge of the signaling mechanisms underlying the differential development of dendrites and axons. That knowledge is needed to develop strategies that will allow preferential or specific manipulations of dendrite or axon development in disease conditions and in animal models to interrogate the functions of the nervous system.
|Zhou, Wei; Chang, Jin; Wang, Xin et al. (2014) GM130 is required for compartmental organization of dendritic golgi outposts. Curr Biol 24:1227-33|
|Wang, Xin; Sterne, Gabriella R; Ye, Bing (2014) Regulatory mechanisms underlying the differential growth of dendrites and axons. Neurosci Bull 30:557-68|
|Yang, Limin; Li, Ruonan; Kaneko, Takuya et al. (2014) Trim9 regulates activity-dependent fine-scale topography in Drosophila. Curr Biol 24:1024-30|
|Wang, Xin; Kim, Jung Hwan; Bazzi, Mouna et al. (2013) Bimodal control of dendritic and axonal growth by the dual leucine zipper kinase pathway. PLoS Biol 11:e1001572|
|Kim, Jung Hwan; Wang, Xin; Coolon, Rosemary et al. (2013) Dscam expression levels determine presynaptic arbor sizes in Drosophila sensory neurons. Neuron 78:827-38|
|Ye, Bing; Kim, Jung Hwan; Yang, Limin et al. (2011) Differential regulation of dendritic and axonal development by the novel Kruppel-like factor Dar1. J Neurosci 31:3309-19|