Dendrite arborization patterns are a hallmark of neuronal type and a critical determinant of neuronal function, influencing the type and number of inputs that a neuron can receive as well as the ability of a neuron to process multiple inputs. As animals grow, dendrite arbors of many neurons must expand proportionally to sustain proper connectivity and maintain coverage of their receptive field. Likewise, large portions of dendrite arbors in adult neurons are stable over extended periods of time to maintain receptive field coverage and patterns of connectivity. However, little is known about how dendrite arbors are actively maintained. Using genetic screens, we have identified mutants that phenotypically define different modes of extrinsic regulation of dendrite maintenance in Drosophila sensory neurons. With this proposal, we aim to test the hypotheses that (1) localized adhesive contacts ensure coordinated expansion of dendrites and their receptive field during times of growth, (2) substrate-derived signals restrict dendrite structural plasticity, preventing dendrite growth beyond normal receptive field boundaries, and (3) substrate-derived trophic signals are continuously required to support dendrite maintenance.
In Aim 1, we will define roles of dendrite-epithelial contacts in coordinating dendrite arbor and receptive field expansion, and identify factors that modulate these contacts. We will monitor these contacts in vivo using a genetically-encoded fluorescence-based proximity sensor, characterize the contacts at high resolution using electron microscopy, test the functional relevance of the contacts by modifying the distribution of the contact sites in the epithelium, and analyze genetic mutants that likely disrupt these contacts.
In Aim 2, we will define roles of substrate extracellular matrix (ECM) modification in restricting dendrite growth and ensuring maintenance of receptive field coverage. We will use genetically encoded markers and electron microscopy to delineate changes in ECM organization and distribution during normal development and in maintenance-defective mutants. Additionally, we will identify substrate-derived factors required for ECM modifications.
In Aim 3, we will define a neuron non-autonomous pathway that regulates trophic signaling for dendrite maintenance. Altogether, these studies will elucidate mechanisms by which growth of dendrites and their substrate are coordinated during growth, ensuring maintenance of dendrite coverage. Although defects in dendrite morphology are associated with a variety of developmental and degenerative disorders, including mental retardation, epilepsy, schizophrenia, and Parkinson's disease, little is known about how dendrite arbors are maintained. Basic insights gained from this work are expected to be of significance for understanding the normal developmental role of different types of extrinsic signals in dendrite maintenance as well as the consequences of perturbing these extrinsic signals.

Public Health Relevance

The proposed research is relevant to public health because dendrite defects are widely associated with developmental and progressive neurological disorders, including mental retardation, epilepsy, schizophrenia, and Parkinson's disease. Remarkably, in many of these disorders, dendrite defects appear after a normal period of early development, suggesting that defects in dendrite maintenance underlie disease pathology. The proposed research will provide understanding of mechanisms involved in maintaining dendrite arbors, and this understanding is essential for developing therapeutic strategies to treat dendrite pathologies in human disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Mamounas, Laura
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University of Washington
Schools of Arts and Sciences
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Jiang, Nan; Kim, Hyeon-Jin; Chozinski, Tyler J et al. (2018) Superresolution imaging of Drosophila tissues using expansion microscopy. Mol Biol Cell 29:1413-1421
Hoyer, Nina; Zielke, Philip; Hu, Chun et al. (2018) Ret and Substrate-Derived TGF-? Maverick Regulate Space-Filling Dendrite Growth in Drosophila Sensory Neurons. Cell Rep 24:2261-2272.e5
Vinauger, Clément; Lahondère, Chloé; Wolff, Gabriella H et al. (2018) Modulation of Host Learning in Aedes aegypti Mosquitoes. Curr Biol 28:333-344.e8
Utashiro, Nao; Williams, Claire R; Parrish, Jay Z et al. (2018) Prior activity of olfactory receptor neurons is required for proper sensory processing and behavior in Drosophila larvae. Sci Rep 8:8580
Yan, Connie; Wang, Fei; Peng, Yun et al. (2018) Microtubule Acetylation Is Required for Mechanosensation in Drosophila. Cell Rep 25:1051-1065.e6
Williams, Claire R; Baccarella, Alyssa; Parrish, Jay Z et al. (2017) Empirical assessment of analysis workflows for differential expression analysis of human samples using RNA-Seq. BMC Bioinformatics 18:38
Boiko, Nina; Medrano, Geraldo; Montano, Elizabeth et al. (2017) TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids. PLoS One 12:e0186888
Williams, Claire R; Baccarella, Alyssa; Parrish, Jay Z et al. (2016) Trimming of sequence reads alters RNA-Seq gene expression estimates. BMC Bioinformatics 17:103
Meltzer, Shan; Yadav, Smita; Lee, Jiae et al. (2016) Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons. Neuron 89:741-55
Lee, Jiae; Peng, Yun; Lin, Wen-Yang et al. (2015) Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw. Development 142:162-73

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