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Printable Handouts
Navigable Slide Index
- Introduction
- Concept of axon guidance
- Brain section of an adult fly
- Process of path finding by growth cones
- A growth cone
- Embryonic nervous system of a fly
- Navigation of a neuron within the VNC
- Receptors and ligands involved in midline crossing
- Frazzled and Robo function in axon guidance
- Midline crossing: WT versus robo / comm mutants
- Schematic structure of Frazzaled and Robo
- Commissure choice and the Derailed receptor
- RYK subfamily of RTKs
- RYK family of receptors
- Classes of Drl-expressing neurons
- Detection of Drl-expressing neurons
- Drl mutants have defects in midline crossing
- Axon-targeted reporters
- Differential labeling using different reporters
- GAL4 / UAS transactivation
- Expressing Drl in eagle neurons
- Midline crossing in Drl-expressing eagle neurons
- Effect of Drl on non-crossing neurons
- Drl functions as mediator of repulsion
- Wnt5
- Wnt5 expression pattern
- Wnt5 mutants resemble Derailed mutants
- Drl requires Wnt5 to switch axons
- Altering Wnt5 expression
- Repulsive activity of Wnt5 is mediated by Drl
- Soluble Drl-Fc extracellular probe binding in vivo
- Wnt5 binding to Drl in vitro
- Possible signaling of Wnt5 through Fz receptor
- Function of mammalian Wnt protein
- Model of midline crossing
- Integration of the signals in the growth cone
- Major points
Topics Covered
- How axons grow
- The growth cone
- The Drosophila nervous system
- Receptors and ligands involved in axon guidance events
- Attractive and repulsive receptor signaling
- Integration of receptor signals in the growth cone
- Conservation of axon guidance mechanisms during evolution
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Thomas, J. (2023, June 19). Axon guidance in Drosophila [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 9, 2024, from https://doi.org/10.69645/FNHL3339.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. John Thomas has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neurology
Transcript
Please wait while the transcript is being prepared...
0:00
I'm J.B Thomas from the Salk Institute.
And in this lecture I'll be talking
about axon guidance in Drosophila.
I'll review the impact that studies in
Drosophila have had on our understanding
of how axons are guided to
their synaptic target cells.
Thus forming the circuits that
make up the nervous system.
And in doing so I hope to give some idea
of how Drosophila has been capitalized on
as a genetic model system
to advance the field.
0:24
The axon guidance field traces its roots
to the great anatomist Ramon y Cajal
who in the late 19th century first
hypothesized that the basic unit
of the nervous system
is the single neuron.
And this led him to think about how
neurons might be assembled during
development.
And the question he posed in
one of his early works is as
much the guiding question of the field
today as it was over 100 years ago.
He wrote, "wherein lies that marvelous
power which enables the nerve fibers from
very distant cells to make contact
directly with certain other nerve cells,
without going astray or
taking a roundabout course?" In essence,
he was asking how the nervous
system wires itself up.
And as he illustrated in many drawings,
Cajal went on to propose that a way
a neuron grows is via the growth
cone at the tip of its axon.
And that the growth cone is endowed with
the ability to sense chemical signals.
And work over the past two decades,
much of it on Drosophila has helped to
elucidate the molecular basis
effects on guidance and
continues to confirm how truly
visionary Cajal's work was.
1:22
In terms of the Drosophila nervous system,
I'd like to start by showing a section
through an adult fly's brain.
Just to give you an indication of how
complicated a tissue it actually is.
This section was stained using a technique
similar to that used by Cajal over
a century ago.
There are over 100,000
neurons in the brain,
only some of which of course
are visible in this section, and
their synaptically connected
with great precision.
The neuronal cell bodies
lie near the periphery.
They're bilaterally symmetric
around the midline.
Essentially everything else in the section
is composed of axonal projections.
And at first glance it
looks a bit disorganized.
But upon further analysis,
you can see that there's a very fine and
regular structure in which neurons project
their axons along specific pathways to
reach in synapse with their targets.
For example, this hypothetical pink
neuron might project this axe on across
the midline from one side to the other,
in order to synapse with its target cells.
And the homologous cell on the other
side would do the same in mirror image.
But what I'll be talking about is how
during development axons are guided to
their specific target destinations,
allowing them to synapse with
their appropriate partners.
We'll be examining these events in the
embryo where there are far fewer cells in
the architecture is much simpler
than it is here in the adult.