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.
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. !
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|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|
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|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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