Axonal growth is mediated by coordinated changes of the actin and microtubule (MT)
cytoskeleton. Ample evidence suggests that members of the formin protein family are
involved in the coordination of these cytoskeletal rearrangements, but the molecular
mechanisms of the formin-dependent actin–microtubule crosstalk remains largely elusive.
Of the six Drosophila formins, DAAM was shown to play a pivotal role during axonal
growth in all stages of nervous system development, while FRL was implicated in axonal
development in the adult brain. Here, we aimed to investigate the potentially redundant
function of these two formins, and we attempted to clarify which molecular activities
are important for axonal growth. We used a combination of genetic analyses, cellular
assays and biochemical approaches to demonstrate that the actin-processing activity
of DAAM is indispensable for axonal growth in every developmental condition. In addition,
we identified a novel MT-binding motif within the FH2 domain of DAAM, which is required
for proper growth and guidance of the mushroom body axons, while being dispensable
during embryonic axon development. Together, these data suggest that DAAM is the predominant
formin during axonal growth in Drosophila, and highlight the contribution of multiple
formin-mediated mechanisms in cytoskeleton coordination during axonal growth.
