IMP Research Report 2002

Figure 1: Crossing the midline. In the Drosophila CNS, some axons cross the midline (like the red axons in A), but others do not (B). Those that do
cross, called commissural axons, cross only once. Comm functions as a switch to control this decision (C). Comm is ON in commissural neurons as
they cross, but OFF in ipsilateral neurons and post-crossing commissural neurons. Comm regulates the sensitivity of axons to the midline repellent Slit
(yellow in C). It does this by controlling the intracellular trafficking of Robo (blue), the Slit receptor.
specific layer of the brain. We continue to look for the
remaining genes, and are beginning to piece together
the molecular pathways and processes that underlie
this exceptional example of neuronal engineering.
grow toward and across the midline. If it is made
inactive (by a mutation), no axon can cross the midline,
resulting in the commissureless phenotype from which
the gene got its name. In ipsilateral neurons, and postcrossing
commissural neurons, Comm is normally
inactive. But by activating Comm in these neurons, we
can force them to cross (or recross). This defines Comm
as a simple genetic switch to control midline crossing
(Figure 1). We are currently trying to find out how this
switch is turned ON and OFF, and how Comm selects
Robo and sorts it to lysosomes.
Axon guidance in the visual system
Flies have excellent vision. This rests in part on the
extraordinarily precise connections established
between photoreceptors in the eye and their targets in
the brain. As a first step in determining how these
connections are established, we screened though more
than 32,000 mutant lines to find some 200 mutants with
Figure 2: Photoreceptor axon targeting. Photoreceptor axons
(green) extend from the eye disc, through the optic stalk, and into
the optic lobe. Some axons terminate in the lamina (arrow). Others,
including R8 axons, terminate in the medulla (arrowhead), where
they form synapses with medulla neurons (red). The Flamingo
protein (blue) is required for correct targeting of R8 axons.
abnormal connectivity patterns. These mutations define
about 50 different genes, 31 of which we have now
identified. These genes encode cell surface receptors
Contact: dickson@imp.univie.ac.at
and signaling molecules, as well as factors involved in
gene transcription, axonal transport, and membrane
trafficking. One of them encodes a 7-transmembrane
cadherin called Flamingo. Flamingo is expressed on
many different photoreceptor axons and their target cells
in the brain (Figure 2). It is needed for one class of
photoreceptors (R8s) to select their correct targets in a
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