Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila

Abstract

The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts.

Polyglutamine repeat proteins disrupt actin structure in Drosophila photoreceptors

“…Notably, frl knockdown caused ommatidial rotation defects, as previously reported ( Fig. 3C) (Dollar et al, 2016). Only knockdown of fhos or form3 caused a reduction of rhabdomere size (ANOVA: f = 42.62, df = (6,63), p < 0.0001) ( Fig.…”

“…Other formins do function in photoreceptors. Frl is required for planar cell polarity in developing eyes, a requirement recapitulated in our studies (Dollar et al, 2016) (Fig. 3D).…”

“…3D). Double mutants of DAAM and Frl have stronger photoreceptor phenotypes than either mutant alone, indicating that DAAM is also active in these cells (Dollar et al, 2016). We found that fhos RNAi also affected rhabdomere size (Fig.…”

Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability

“…This constitutes a new role for the Frl/Fmnl formin since so far it has been mainly described as participating to the lamellipodia/filopodia formation 41–44 . It would be interesting to know if, like in other systems, Frl is regulated by either Cdc42 41, 44, 45 or Rac1 46 to promote the persistent network assembly. Furthermore, it is likely that other formins participate to the persistent network assembly, especially in the germband since the lack of Frl (frl 59/59 ) only partially reduces the network density (see Fig.…”

“…4b). The DAAM formin would constitute a first good candidate since it has been shown that DAAM and Frl cooperate during axon growth in the mushroom bodies of Drosophila 45 .…”