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CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab

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Cell Biology of the Neuron: <strong>Polarity</strong>, Plasticity and Regeneration, Crete 2011<br />

RNA-Binding Protein Hermes Regulates Axon<br />

Guidance and Branching in the Developing Visual<br />

System<br />

Hanna Hornberg, Daniel Maurus, Francis Wollerton-van Horck, Maarten Zwart,<br />

William Harris, Christine Holt<br />

Department of Physiology, Development and Neuroscience, University of<br />

Cambridge, Downing St, CB2 3DY, Cambridge, UK<br />

In the developing visual system, retinal ganglion cells (RGCs) project<br />

topographically along the anterior-posterior (A-P) and dorsal-ventral (D-V) axes<br />

to their target area in the optic tectum, where they arborize and form synaptic<br />

connections. The formation of this circuit is tightly regulated both by extracellular<br />

guidance cues in the environment, and by intracellular processes in the RGC<br />

axons such as RNA localization and translation. Here, we reveal the functional<br />

role of the RNA-binding protein Hermes (also known as RBPMS) in retinal axon<br />

navigation in vivo. Hermes is expressed exclusively in RGCs in the CNS and is<br />

present in their growing axons and growth cones where it localises in granules.<br />

Antisense morpholino knockdown of Hermes in embryonic zebrafish caused<br />

axons along the D-V axis to make positional errors in the optic tract, and to enter<br />

the tectum through an indirect route . Axons also failed to map correctly along the<br />

A-P axis. Furthermore, Hermes knockdown in both zebrafish and Xenopus<br />

significantly impaired retinal axon branching in the tectum. Overexpression of a<br />

dominant negative Hermes protein defective in a domain required for granular<br />

localisation in Xenopus also impaired branching, suggesting that proper<br />

localization of Hermes is critical to its function. These results show that Hermes<br />

contributes to both mapping and arborisation and suggests an important role in<br />

several aspects of circuit formation.<br />

Presented by: Hornberg, Hanna<br />

Poster No 050<br />

Green Session<br />

132

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