Recent studies established that the planar cell polarity (PCP) pathway is critical
for various aspects of nervous system development and function, including axonal guidance.
Although it seems clear that PCP signaling regulates actin dynamics, the mechanisms
through which this occurs remain elusive. Here, we establish a functional link between
the PCP system and one specific actin regulator, the formin DAAM, which has previously
been shown to be required for embryonic axonal morphogenesis and filopodia formation
in the growth cone. We show that dDAAM also plays a pivotal role during axonal growth
and guidance in the adult Drosophila mushroom body, a brain center for learning and
memory. By using a combination of genetic and biochemical assays, we demonstrate that
Wnt5 and the PCP signaling proteins Frizzled, Strabismus, and Dishevelled act in concert
with the small GTPase Rac1 to activate the actin assembly functions of dDAAM essential
for correct targeting of mushroom body axons. Collectively, these data suggest that
dDAAM is used as a major molecular effector of the PCP guidance pathway. By uncovering
a signaling system from the Wnt5 guidance cue to an actin assembly factor, we propose
that the Wnt5/PCP navigation system is linked by dDAAM to the regulation of the growth
cone actin cytoskeleton, and thereby growth cone behavior, in a direct way.