Two Frizzled Planar Cell Polarity Signals in the Drosophila Wing Are Differentially Organized by the Fat/Dachsous Pathway

Abstract

The regular array of distally pointing hairs on the mature Drosophila wing is evidence for the fine control of Planar Cell Polarity (PCP) during wing development. Normal wing PCP requires both the Frizzled (Fz) PCP pathway and the Fat/Dachsous (Ft/Ds) pathway, although the functional relationship between these pathways remains under debate. There is strong evidence that the Fz PCP pathway signals twice during wing development, and we have previously presented a Bidirectional-Biphasic Fz PCP signaling model which proposes that the Early and Late Fz PCP signals are in different directions and employ different isoforms of the Prickle protein. The goal of this study was to investigate the role of the Ft/Ds pathway in the context of our Fz PCP signaling model. Our results allow us to draw the following conclusions: (1) The Early Fz PCP signals are in opposing directions in the anterior and posterior wing and converge precisely at the site of the L3 wing vein. (2) Increased or decreased expression of Ft/Ds pathway genes can alter the direction of the Early Fz PCP signal without affecting the Late Fz PCP signal. (3) Lowfat, a Ft/Ds pathway regulator, is required for the normal orientation of the Early Fz PCP signal but not the Late Fz PCP signal. (4) At the time of the Early Fz PCP signal there are symmetric gradients of dachsous (ds) expression centered on the L3 wing vein, suggesting Ds activity gradients may orient the Fz signal. (5) Localized knockdown or over-expression of Ft/Ds pathway genes shows that boundaries/gradients of Ft/Ds pathway gene expression can redirect the Early Fz PCP signal specifically. (6) Altering the timing of ds knockdown during wing development can separate the role of the Ft/Ds pathway in wing morphogenesis from its role in Early Fz PCP signaling.

Regulation of long-range planar cell polarity by Fat-Dachsous signaling

“…This regulation occurs through controlling directed changes in cell shape, movement and oriented division, and microtubule dynamics upstream of Fz/PCP signaling (Aigouy et al, 2010;Harumoto et al, 2010;Hogan et al, 2011;Sagner et al, 2012).…”

“…The wing surface is folded in shallow peaks and troughs called cuticle ridges (Doyle et al, 2008;Hogan et al, 2011). These are also planar polarized: in the wing blade anterior to longitudinal vein 3 (L3), ridges are aligned along the anterio-posterior (A-P) axis, and in the wing blade posterior to L3, ridges are aligned along the proximo-distal (P-D) axis.…”

“…Furthermore, mosaic analysis suggests that biasing of R3/4 fate specification by ft The interaction between the two pathways also varies by tissue. In the Drosophila wing, Ft-Ds signaling is mostly upstream of Fz/PCP activity (Adler et al, 1998;Aigouy et al, 2010;Harumoto et al, 2010;Hogan et al, 2011;Ma et al, 2003;Matakatsu and Blair, 2004;Sagner et al, 2012). In the abdomen Ft-Ds and Fz/PCP act in parallel (Casal et al, 2006), with each pathway able to regulate polarity while the other is disrupted.…”

“…The relationship between The Ft-Ds and Fz/PCP pathways is complex and context-dependent (Adler et al, 1998;Aigouy et al, 2010;Casal et al, 2006;Hogan et al, 2011;Ma et al, 2003;Matakatsu and Blair, 2004;Sagner et al, 2012;Strutt and Strutt, 2002;Yang et al, 2002). ft clones and ds clones expressing fz-RNAi had no consistent rescue or reversal of polarity inside clones.…”

“…Both pathways display intracellular asymmetry of their components, and each can maintain this asymmetry in the absence of the other (Ambegaonkar et al, 2012;Brittle et al, 2012;Yang et al, 2002). In both the wing and the eye, the relationship between Ft-Ds and Fz/PCP also changes at different times in development (Hogan et al, 2011;Strutt and Strutt, 2002). Their relationship is thus complex, and is unlikely to be resolved without determination of the actual mechanisms that comprise the largely phenomenological concepts of "ft activity" and "fz activity".…”