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

Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011
RNA-Based Control of Visual System Wiring
Christine Holt
University of Cambridge
Axon guidance is a key step in wiring the brain. To establish neural circuits, the
axons of differentiating neurons must navigate accurately to distant targets and
select precise synaptic partners. We are trying to understand the mechanisms that
underlie these highly selective processes in the vertebrate visual system.
Emerging evidence points to an increasingly important role for posttranscriptional
mechanisms such as RNA localization and local protein synthesis.
Sub-cellular profiling shows that axonal growth cones contain a remarkably
diverse repertoire of mRNAs that are dynamically regulated with age. In vitro
functional assays reveal that directional turning responses of growth cones to
some guidance cues depend on local protein synthesis. Our studies support a
‘differential translation model’ for axon steering in which attractive and repulsive
cues induce opposite turning behaviours through eliciting translation of distinct
mRNAs. An important component of this cue-induced translation is that it can be
controlled with high spatial precision enabling localized sub-cellular responses. A
polarised cue, for example, triggers protein synthesis on the near-stimulus side of
the 5 micron growth cone that is achieved through co-ordinately regulated
asymmetries in receptor activation, mRNA trafficking and translation activation.
Our functional studies of specific RNA-binding proteins are beginning to provide
in vivo evidence that RNA-based mechanisms play a pre-synaptic role in the
establishment and the topographic arrangement of synaptic connections in the
visual system.
Presented by: Holt, Christine
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