Polarity determination in the Drosophila eye: a novel role for Unpaired and JAK/STAT signaling

Abstract

The JAK/STAT signaling pathway is required for many processes including cytokine signaling, hematopoiesis, gliagenesis, and Drosophila segmentation. In this report we present evidence demonstrating that the JAK/STAT pathway is also central to the establishment of planar polarity during Drosophila eye development. We show that a localized source of the pathway ligand, Unpaired, is present at the midline of the developing eye, which is capable of activating the JAK/STAT pathway over long distances. A gradient of JAK/STAT activity across the DV axis of the eye regulates ommatidial polarity via an unidentified second signal. Additionally, localized Unpaired influences the position of the equator via repression of mirror.

The roles of the Drosophila JAK/STAT pathway

“…The activity of the reporter is inversely proportional to the actual level of JAK/ STAT pathway activity. Clones of cells mutant for hop result in up-regulation of STAT-lacZ while clones of cells ectopically expressing upd strongly downregulate STAT-lacZ, not only within the region of Upd mis-expression, but also in surrounding tissues (Zeidler et al, 1999b). Based on these ®ndings, it is clear that the pattern of STAT-lacZ in the wild type situation can be used to indicate the level of JAK/ STAT pathway signaling.…”

“…Based on these ®ndings, it is clear that the pattern of STAT-lacZ in the wild type situation can be used to indicate the level of JAK/ STAT pathway signaling. Such an analysis shows that a clear gradient of JAK/STAT pathway activity exists across the developing eye primordia with highest activity at the midline of the eye imaginal disc and (Zeidler et al, 1999b;H Sun, personal communication). This ®nding represents one of the clearest correlations between the pattern of Upd and the resultant activity of the JAK/STAT pathway in vivo, further strengthening the link between Upd and its role in the activation of the JAK/STAT pathway.…”

“…Furthermore, tissue culture experi- (Harrison et al, 1998). Taken together with in vivo evidence showing that Upd functions as an activator of JAK/STAT signaling in the eye (Zeidler et al, 1999b), it is clear that Unpaired represents a bona ®de JAK/STAT pathway ligand.…”

“…The existence of nonautonomous ommatidial inversion phenotypes has been interpreted to suggest that both the JAK/STAT and Wingless pathways, cannot be acting directly, but rather must be exerting their e ects via the production of one or more intermediate molecules of signaling pathways capable of acting at a distance. These factors have been given various names including, the`second signal' (the term we shall use in this review), factor X and Wnt X (Papayannopoulos et al, 1998;Wehrli and Tomlinson, 1998;Zeidler et al, 1999b). The identity of a putative second signal has remained elusive despite the fact that a number of predictions regarding the molecular nature and expression pattern of the second signal can be made (Zeidler et al, 1999b).…”

“…These factors have been given various names including, the`second signal' (the term we shall use in this review), factor X and Wnt X (Papayannopoulos et al, 1998;Wehrli and Tomlinson, 1998;Zeidler et al, 1999b). The identity of a putative second signal has remained elusive despite the fact that a number of predictions regarding the molecular nature and expression pattern of the second signal can be made (Zeidler et al, 1999b). However, a recent report has described the identi®cation of such a molecule (Zeidler et al, 1999a).…”