Splits ends is a tissue/promoter specific regulator of Wingless signaling

Abstract

Wingless directs many developmental processes inDrosophila by regulating expression of specific target genes through a conserved signaling pathway. Although many nuclear factors have been implicated in mediating Wingless-induced transcription, the mechanism of how Wingless regulates different targets in different tissues remains poorly understood. We report here that the split ends gene is required for Wingless signaling in the eye, wing and leg imaginal discs. Expression of a dominant-negative version of split ends resulted in more dramatic reductions in Wingless signaling than split ends-null alleles, suggesting that it may have a redundant partner. However, removal of split ends or expression of the dominant-negative had no effect on several Wingless signaling readouts in the embryo. The expression pattern of Split ends cannot explain this tissue-specific requirement, as the protein is predominantly nuclear and present throughout embryogenesis and larval tissues. Consistent with its nuclear location, the split ends dominant-negative acts downstream of Armadillo stabilization. Our data indicate that Split ends is an important positive regulator of Wingless signaling in larval tissues. However, it has no detectable role in the embryonic Wingless pathway, suggesting that it is a tissue or promoter-specific factor.

Characterization of the split ends-Like Gene spenito Reveals Functional Antagonism Between SPOC Family Members During Drosophila Eye Development

“…Because the large SPOC family member spen is required for Drosophila eye development (Dickson et al 1996;Rebay et al 2000;Lin et al 2003) and the fly eye provides a uniquely powerful system in which to explore functional relationships between signaling molecules (Zipursky and Rubin 1994), we focused our analyses on this tissue. RT-PCR confirmed that nito, like spen, is expressed in the developing eye disc (Figure 4 and data not shown), further validating the approach.…”

“…Next, we investigated the consequences of increasing or decreasing nito levels in the background of a dominant negative spen transgene (spen DN ), which encodes the C-terminal 936 amino acids of spen (Lin et al 2003) and also produces dose-sensitive phenotypes (D. Doroquez and I. Rebay, unpublished results). Because both transgenes are capable of perturbing eye development on their own, to distinguish between additive and synergistic interactions we used a NITO-FL transgenic line that when expressed with sev weak exhibits only very mild perturbations of the adult eye ( Figure 4A).…”

“…In addition to its role in RTK-mediated signaling events, spen functions as a context-specific positive regulator of Wingless signaling and as a likely regulator of Notch signaling (Oswald et al 2002;Schreiber et al 2002;Kuroda et al 2003;Lin et al 2003). Together these results suggest a complex role for SPEN as a nuclear effector and potential integrator of multiple signaling pathways.…”

“…; sev med -Gal4, UASspen DN (Lin et al 2003); sev-Gal4 (weak and medium generated by I. Rebay and strong from Bloomington Stock Center); spen xfm911 /Cyo . Western blots: Western blot to examine expression of UASnito transgenes was carried out by crossing UAS lines to hsp70Gal4, heat-shocking adults for 1 hr, followed by a 1.5 hr recovery.…”

spenito is required for sex determination in Drosophila melanogaster

“…Subsequent studies found that spen is implicated in a variety of cellular and developmental processes including neuronal cell fate specification, axon guidance, cell cycle, Hox gene regulation, and cell death (27)(28)(29)(30). These pleiotropic effects are likely due to the involvement of spen in multiple signaling pathways (31)(32)(33). However, the molecular mechanisms underlying the function of Spen in these pathways are not understood.…”