The targeting of axons and dendrites is essential for proper wiring of the nervous system and the expression of behavior. To understand how the nervous system is wired during development we focus on cell-cell interactions that underlie specificity in wiring the somatosensory system. Somatosensation is important for sensing touch and noxious stimuli, and for driving distinct and appropriate behavioral responses. We focus on the influence of local axon-axon interactions in circuit organization, function, and behavior. The somatosensory system of Drosophila is an excellent model to probe the cellular and molecular basis for neural circuit wiring and function. Here we focus on the developmental mechanisms that ensure robust axon segregation to different parts of the nervous system and how these patterns ensure appropriate neural circuit functioning. Many of the developmental processes under study, including axon-axon adhesion, repulsion, refinement, axon target selection, and the control of these processes by molecular cues and neural activity, are central to nervous system development in other species. We find that the positioning of somatosensory axons is highly ordered in the Drosophila central nervous system. This precise ordering appears to ensure that different qualities of sensory information are passed to correct downstream circuits and lead to appropriate behavioral responses. We propose that developing axons that are responsible for sensing different modalities engage in interactions that ensure separation of connections and distinct behaviors in response to sensory stimulation. By contrast we propose that axons of the same modality may engage in positive attractive interactions that ensure cohesion during wiring.
We aim to test the developmental mechanisms that enforce the normally robust and distinct relationships between sensory input and motor output. We propose that at least part of the mechanism lies in a hierarchy of developmental axon-axon interactions between different sensory modalities and that understanding how this orderly wiring emerges will provide insights into the mechanisms by which nervous systems are patterned more generally, and how patterning might be disrupted in developmental disorders of the nervous system.

Public Health Relevance

Cell-cell interactions are critical for wiring neural circuits, however the principles of these interactions and effects on behavior are still not completely understood. We propose to study interactions occurring between axons, and between axons and dendrites, at several stages of their development in the high-resolution Drosophila somatosensory system. Principles that are discovered hold promise for uncovering similar action in other systems and their importance for fidelity in nervous system wiring and behavior. !

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS061908-13
Application #
10006606
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lavaute, Timothy M
Project Start
2008-04-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
13
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Physiology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Burgos, Anita; Honjo, Ken; Ohyama, Tomoko et al. (2018) Nociceptive interneurons control modular motor pathways to promote escape behavior in Drosophila. Elife 7:
Qian, Cheng Sam; Kaplow, Margarita; Lee, Jennifer K et al. (2018) Diversity of Internal Sensory Neuron Axon Projection Patterns Is Controlled by the POU-Domain Protein Pdm3 in Drosophila Larvae. J Neurosci 38:2081-2093
Corty, Megan M; Tam, Justina; Grueber, Wesley B (2016) Dendritic diversification through transcription factor-mediated suppression of alternative morphologies. Development 143:1351-62
Bouchard, Matthew B; Voleti, Venkatakaushik; Mendes, César S et al. (2015) Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms. Nat Photonics 9:113-119
Singhania, Aditi; Grueber, Wesley B (2014) Development of the embryonic and larval peripheral nervous system of Drosophila. Wiley Interdiscip Rev Dev Biol 3:193-210
Ziegenfuss, Jennifer S; Grueber, Wesley B (2013) SAX-7 and menorin light the path for dendrite morphogenesis. Cell 155:269-71
Hoang, Phuong; Grueber, Wesley B (2013) Dendritic self-avoidance: protocadherins have it covered. Cell Res 23:323-5
Zipursky, S Lawrence; Grueber, Wesley B (2013) The molecular basis of self-avoidance. Annu Rev Neurosci 36:547-68
Kim, Michelle E; Shrestha, Brikha R; Blazeski, Richard et al. (2012) Integrins establish dendrite-substrate relationships that promote dendritic self-avoidance and patterning in drosophila sensory neurons. Neuron 73:79-91
Shrestha, Brikha R; Grueber, Wesley B (2011) Methods for exploring the genetic control of sensory neuron dendrite morphogenesis in Drosophila. Cold Spring Harb Protoc 2011:910-6

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