The frizzled/stan pathway and planar cell polarity in the Drosophila wing

Abstract

Drosophila has been the key model system for studies on planar cell polarity (PCP). The rich morphology of the insect exoskeleton contains many structures that display PCP. Among these are the trichomes (cuticular hairs) that cover much of the exoskeleton, sensory bristles, and ommatidia. Many genes have been identified that must function for the development of normal PCP. Among these are the genes that comprise the frizzled/starry night (fz/stan) and dachsous/fat pathways. The mechanisms that underlie the function of the fz/stan pathway are best understood. All of the protein products of these genes accumulate asymmetrically in wing cells and there is good evidence that this involves local intercellular signaling between protein complexes on the distal edge of one cell and the juxtaposed proximal edge of its neighbor. It is thought that a feedback system, directed transport, and stabilizing protein-protein interactions mediate the formation of distal and proximal protein complexes. These complexes appear to recruit downstream proteins that function to spatially restrict the activation of the cytoskeleton in wing cells. This leads to the formation of the array of distally pointing hairs found on wings.

Figure 1

Hair Polarity on the fly wing. Panel A shows the polarity of hairs on the dorsal surface of a wild type wing. Panel B shows the stereotypic pattern seen on the dorsal surface of an inturned wing. The blackened area is where the polarity was too variable to draw a consensus vector. Panel C shows images of wings from two regions (noted in panel A) of Oregon R, fz, in and mwh mutant wings. Note the relative similarity of the polarity patterns. The downstream genes ofetn show a slightly stronger polarity disruption, but with similar directionality. Panel D shows a fz clone marked by the cell marker strb (causes short deformed and multipled hairs). Panel E a pk clone marked by sha (causes a loss of hairs) and Panel F a Vang clone marked by sha. Arrows show local hair polarity.

Figure 2

Polarized protein accumulation and mutant phenotypes. Panel A shows cartoons of wild type and mutant cells. In the wild type cell all of the fz/stan pathway proteins accumulate asymmetrically and hairs are formed at the distal vertex. In cells mutant for fz or other core genes hairs form at a relatively central location and no proteins accumulate asymmetrically. In cells mutant for in or any of the other PPE genes multiple hairs form at an abnormal location on the cell periphery. The core proteins accumulate asymmetrically but the PPE proteins and Mwh do not. In cells mutant for mwh genes multiple hairs form at an abnormal location on the cell periphery. The core and PPE proteins accumulate asymmetrically but Mwh does not. Panel B shows the accumulation of Fz-GFP by direct imaging opf GFP (green) (no immunostaining) and actin in red (hairs). Panel C shows the coordinate asymmetric accumulation of Fz (green) and In (red).

Figure 3

Bristles and PCP. Panel A is an SEM of a wild type thorax and panel B a fz thorax. Panel C is a wild type femur and panel D a fz femur. Arrows point to bracts. Panel E is a wild type tarsus and panel F a fz tarsus. The arrow points to a segment with a mirror image duplication and the arrowhead to a bulge.

Figure 4

The eye and PCP. Panel A is a cartoon of the adult retina with Northern (blue) and Southern (red) hemisphere ommatidia in mirror image across the equator. Panel B shows how the pattern in the adult retina is derived by rotation of the developing retina. The crucial R3 (blue) and R4 (green) cells are marked.

Figure 5

Less well known PCP related phenotypes. Panels A and B show wild type and fz pupae respectively. In a modest fraction of fz pupae the wing everts forward instead of posteriorly (as shown in B). Arrowheads point to the eye and arrows to the wing hinge region. Panel C is a wild type wing and Panel D is a distorted wing that results from the abnormal eversion as shown in B. Panel EFG are wings imaged by Cuticle Reflection microscopy (E) and normal bright field microscopy (G) and a merged image (F). These panels were generously provided by S. Collier. Panel H is a wild type wing and panel I the same region of a wing from a fly homozygous for a mutation in Gliotactin. Note the lack of parallel alignment of neighboring hairs in I.

Figure 6

A possible model for PCP protein action in wing cells. Two neighboring cells are diagrammed. Proteins on the distal membrane of one cell (Fz and Stan) interact with proteins on the proximal membrane of the neighboring cell (Vang and Stan). The core transmembrane proteins recruit the cytoplasmic core proteins (Dsh, Dgo and Pk). The PPE proteins are recruited to the proximal side where In recruits Mwh. Mwh inhibits the actin cytoskeleton in the distal part of the cell. Dsh activates an activator of the actin cytoskeleton distally. For simplicity only one of the feedback interactions between cytoplasmic proteins is drawn (Pk inhibiting Dsh on the distal side).