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Julie Simpson

Simpson Lab
Lab Head
Contact Me

The projects in my lab seek to identify the neurons and circuits required to drive complex innate behavioral sequences.  With suitable genetic access to relevant neurons, we study how these neurons act within networks to evaluate multiple inputs and produce appropriate outputs.  Building better tools for imaging and manipulating neurons facilitates these circuit mapping endeavors

Education

AB Princeton Molecular Biology (Hiromi lab) 1995

Ph.D. University of CA Berkeley (Goodman lab) 2001

Post-doc University of WI Madison (Ganetzky lab) 2001-2006

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Publications

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Janelia Publications

Mapping and manipulating neural circuits in the fly brain.
Advances in Genetics 2009 J. H. Simpson Advances in Genetics, 65:79-143 (2009)
doi:10.1016/S0065-2660(09)65003-3

Drosophila is a marvelous system to study the underlying principles that govern how neural circuits govern behaviors. The scale of the fly brain (approximately 100,000 neurons) and the complexity of the behaviors the fly can perform make it a tractable experimental model organism. In addition, 100 years and hundreds of labs have contributed to an extensive array of tools and techniques that can be used to dissect the function and organization of the fly nervous system. This review discusses both the conceptual challenges and the specific tools for a neurogenetic approach to circuit mapping in Drosophila.

application/pdf iconAdvances in Genetics, Volume 65, 2009 , Pages 79-143 .pdf

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Prior Publications (4)

Prior Publications (4)

Ectopic expression in the giant fiber system of Drosophila reveals distinct roles for roundabout (Robo), Robo2, and Robo3 in dendritic guidance and synaptic connectivity.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 2002 T. A. Godenschwege, J. H. Simpson, X. Shan, G. J. Bashaw, C. S. Goodman, and R. K. Murphey The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 22:3117-29 (2002)
doi:20026291

The Roundabout (Robo) receptors have been intensively studied for their role in regulating axon guidance in the embryonic nervous system, whereas a role in dendritic guidance has not been explored. In the adult giant fiber system of Drosophila, we have revealed that ectopic Robo expression can regulate the growth and guidance of specific motor neuron dendrites, whereas Robo2 and Robo3 have no effect. We also show that the effect of Robo on dendritic guidance can be suppressed by Commissureless coexpression. Although we confirmed a role for all three Robo receptors in giant fiber axon guidance, the strong axon guidance alterations caused by overexpression of Robo2 or Robo3 have no effect on synaptic connectivity. In contrast, Robo overexpression in the giant fiber seems to directly interfere with synaptic function. We conclude that axon guidance, dendritic guidance, and synaptogenesis are separable processes and that the different Robo family members affect them distinctly.

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Switching repulsion to attraction: changing responses to slit during transition in mesoderm migration.
Science 2001 S G. Kramer, T. Kidd, J H. Simpson, and C S. Goodman Science, 292:737-40 (2001)
doi:10.1126/science.1058766

Slit is secreted by cells at the midline of the central nervous system, where it binds to Roundabout (Robo) receptors and functions as a potent repellent. We found that migrating mesodermal cells in vivo respond to Slit as both an attractant and a repellent and that Robo receptors are required for both functions. Mesoderm cells expressing Robo receptors initially migrate away from Slit at the midline. A few hours after migration, these same cells change their behavior and require Robo to extend toward Slit-expressing muscle attachment sites. Thus, Slit functions as a chemoattractant to provide specificity for muscle patterning.

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Short-range and long-range guidance by Slit and its Robo receptors: a combinatorial code of Robo receptors controls lateral position.
Cell 2000 J H. Simpson, K S. Bland, R D. Fetter, and C S. Goodman Cell, 103:1019-32 (2000)

Slit is secreted by midline glia in Drosophila and functions as a short-range repellent to control midline crossing. Although most Slit stays near the midline, some diffuses laterally, functioning as a long-range chemorepellent. Here we show that a combinatorial code of Robo receptors controls lateral position in the CNS by responding to this presumptive Slit gradient. Medial axons express only Robo, intermediate axons express Robo3 and Robo, while lateral axons express Robo2, Robo3, and Robo. Removal of robo2 or robo3 causes lateral axons to extend medially; ectopic expression of Robo2 or Robo3 on medial axons drives them laterally. Precise topography of longitudinal pathways appears to be controlled by a combination of long-range guidance (the Robo code determining region) and short-range guidance (discrete local cues determining specific location within a region).

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