Neuroscience 2000 Abstract
Presentation Number: | 108.10 |
---|---|
Abstract Title: | Role reversal of EphB proteins as retinal axon guidance cues. |
Authors: |
Birgbauer, E.*1
; Oster, S.1
; Sretavan, D.1
1Depts. of Ophthalmology & Physiology, U. C. San Francisco, San Francisco, CA |
Primary Theme and Topics |
A. Development and Regeneration - 7. Axon guidance mechanisms and pathways |
Secondary Theme and Topics | A. Development and Regeneration<br />- 6. Process outgrowth, growth cones and sprouting |
Session: |
108. Axon guidance mechanisms and pathways I Slide |
Presentation Time: | Sunday, November 5, 2000 3:15 PM-3:30 PM |
Location: | Room 288 |
Keywords: | Retinal Ganglion Cell, Growth Cone, Receptor Tyrosine Kinase, Pathfinding |
The Eph family of receptor tyrosine kinases has been implicated in a number of developmental processes, including axonal pathfinding. Previously, we demonstrated that retinal axon guidance to the optic disc in mouse involves EphB receptors. However, in addition to their roles as receptors, evidence from biochemical and cell mixing experiments show that Eph molecules may serve as ligands by a reverse signaling mechanism. This mechanism may be acting in the retina since animals lacking both EphB3 and EphB2 proteins have increased axon guidance errors to the disc compared to animals lacking EphB3 but expressing the EphB2 extracellular domain without the kinase domain. To test directly whether retinal axon growth cones respond to EphB extracellular domains, we employed a substrate choice assay using fusion proteins with the extracellular domain of EphB1, B2, or B3 fused to the IgG Fc domain. Results showed that embryonic mouse retinal axons preferred to grow on laminin compared to laminin plus EphB extracellular domains. To investigate the underlying mechanism, we used time-lapse video microscopy to study retinal growth cone responses to soluble EphB-Fc proteins applied in a gradient fashion by pressure-pulse ejection via glass pipettes. Upon exposure to EphB-Fc molecules, retinal growth cones exhibited a range of responses including collapse, decrease in growth rate, or cessation of activity. Furthermore, retinal axons may respond differently to specific EphB class members. Thus, in addition to the role of EphB molecules as guidance receptors, their extracellular domains can act as retinal axon guidance cues by altering growth cone behavior.
Supported by NIH 10688
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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