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.

Public Health Relevance

How the information-receiving (dendrites) and ?sending (axons) parts of neurons form is poorly understood. This knowledge is important because many neurological and psychiatric diseases involve defects in these two parts of neurons. The proposed research will provide the knowledge needed to develop therapeutic strategies having subcellular precision to correct defective dendrites and axons in human diseases.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Panchision, David M
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University of Michigan Ann Arbor
Anatomy/Cell Biology
Schools of Medicine
Ann Arbor
United States
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Sterne, Gabriella R; Kim, Jung Hwan; Ye, Bing (2015) Dysregulated Dscam levels act through Abelson tyrosine kinase to enlarge presynaptic arbors. Elife 4:
Wang, Xin; Zhang, Macy W; Kim, Jung Hwan et al. (2015) The Kr├╝ppel-Like Factor Dar1 Determines Multipolar Neuron Morphology. J Neurosci 35:14251-9
Kaneko, Takuya; Ye, Bing (2015) Fine-scale topography in sensory systems: insights from Drosophila and vertebrates. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 201:911-20
Sanders, Jonathan; Singh, Anil; Sterne, Gabriella et al. (2015) Learning-guided automatic three dimensional synapse quantification for drosophila neurons. BMC Bioinformatics 16:177
Smafield, Timothy; Pasupuleti, Venkat; Sharma, Kamal et al. (2015) Automatic Dendritic Length Quantification for High Throughput Screening of Mature Neurons. Neuroinformatics 13:443-58
Zhou, Wei; Chang, Jin; Wang, Xin et al. (2014) GM130 is required for compartmental organization of dendritic golgi outposts. Curr Biol 24:1227-33
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; Sterne, Gabriella R; Ye, Bing (2014) Regulatory mechanisms underlying the differential growth of dendrites and axons. Neurosci Bull 30:557-68
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

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