The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification

Abstract

The clonal phenotypes, time of requirement and regulation of four-jointed are consistent with it acting in ommatidial polarity determination as a second signal downstream of Notch, JAK/STAT and Wingless. Interestingly, it appears to act redundantly with unknown factors in this process, providing an explanation for the previous failure to identify a second signal.

The roles of the Drosophila JAK/STAT pathway

“…Four jointed (Fj) is a putative secreted type II trans-membrane molecule that is expressed in a broad gradient across the developing eye (Figure 3c; Brodsky and Steller, 1996;Villano and Katz, 1995). Both fj gain-and loss-of-function clones produce ommatidial inversion phenotypes as predicted for a di usible second signal proposed to be downstream of the Wingless and JAK/STAT pathways (Zeidler et al, 1999a). Interestingly, fj expression is regulated by both Upd and the JAK/STAT pathway as would be expected of a bona ®de second signal.…”

“…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). Four jointed (Fj) is a putative secreted type II trans-membrane molecule that is expressed in a broad gradient across the developing eye (Figure 3c; Brodsky and Steller, 1996;Villano and Katz, 1995).…”

“…Indeed analysis of eve expression in mutant embryos indicates that while the JAK/STAT pathway is undoubtedly important in the regulation of eve stripe 3 expression, additional signals feed in to maintain low levels of eve expression in this third stripe even in the total absence of JAK/STAT activity (Hou et al, 1996;Yan et al, 1996a). In addition the proper expression of fj in the developing eye is not simply a consequence of Upd/JAK/STAT signaling but rather appears to require the additional involvement of Wingless signaling, Notch activity and an as yet uncharacterized component of fj autocrine feedback (Zeidler et al, 1999a). No doubt similar complications will arise with regard not only to JAK/STAT signaling, but a wide range of signal transduction responses as the tools available and our resultant understanding of the systems being analysed continue to improve.…”

Developmental expression of the chick four‐jointed homologue

“…Expression is graded being highest in the distal wing/leg, and misexpression studies have demonstrated that fj is sufficient to direct ectopic joint formation (Brodsky and Stellar, 1996;Buckles et al, 2001;Strutt et al, 2004). In addition in Drosophila, fj controls planar polarity, determining the orientation of the bristles/hairs in the wing, leg, and anterior abdomen, and in the eye, the polarity of the ommatidia (Zeidler et al, 1999a(Zeidler et al, ,b, 2000Yang et al, 2002;Simon, 2004). Fj has also been implicated in vein patterning in the wing (Zeidler et al, 2000;Casal et al, 2002).…”

“…It has been proposed that fj is a type II transmembrane glycoprotein, and in support of this, it has been shown that it can be proteolytically cleaved, giving rise to a secreted protein lacking the N-terminus (Villano and Katz, 1995;Buckles et al, 2001). Truncated forms of fj have also been identified in the medium of fj-expressing Drosophila S2 cells, and misexpression studies in Drosophila have shown that fj can act non-cell-autonomously (Tokunaga and Gerhart, 1976;Zeidler et al, 1999aZeidler et al, ,b, 2000Buckles et al, 2001). However, other studies have shown that it does not have to be secreted to have full activity; indeed, Golgi-localized fj was found to have higher activity than secreted forms, suggesting that it modulates the function/processing of other proteins such as ds and ft (Strutt et al, 2004).…”