Wingless

{Models}

Symbol: wg	Flybase ID: {Flybase_ID}
Synonyms: {Name}	{GadFly}
Function: {Short_Function}	{LocusLink}
Keywords: {Keywords}	{Interactive_Fly}

{Summary}

During second larval instar, N and Wg define the DV boundary, which will eventually give rise to a specialised vein structure: the wing margin.
mediate the organizing activity of the DV boundary (Diaz-Benjumea and Cohen, 1995)
Wingless has two distinct functions in cuticle patterning in the embryo: 1. an early function is to maintain engrailed expression (DiNardo, 1988; Martinez-Arias, 1988), which regulates Hh expression that affects cuticular patterning (Heemskerk, 1994). 2. Activation of the wingless pathway is necessary (Bejsovec, 1991) and sufficient (Noordermeer, 1994; Lawrence, 1996) for the formation of naked cuticle.
Wingless signaling is required for naked cuticle but not for denticle belts (Sanson, 1999)

Cubitus interruptus
- The posterior barrier effect of Wg in the embryo is due to Hedgehog signaling since the cuticle phenotype of en-Gal4/UAS-wg; ci^- embryos is identical to that of en-Gal4/UAS-wg; hh^- embryos (Figure 5G). This requirement is dose sensitive, since in hedgehog or cubitus interruptus heterozygotes, Wingless produced in the engrailed domain generates occasional breaches of naked cuticle in the denticle belts (Figures 5H and 5K ). (Sanson, 1999)
DE-Cadherin
- Armadillo is titrated out of its signaling pool when DE-Cadherin is overexpressed, and in the embryonic epidermis, this leads to a phenocopy of a wingless mutation (Sanson, 1996).
  - Overexpressed Cadherin blocks the response to Wingless in a cell-autonomous manner
- clones of cells expressing DE-Cadherin, which blocks wg signaling, located in naked regions make ectopic denticles. Clones within the denticle belts have no effect (Sanson, 1999)
fused
- in a fu mutant there is no expression of wg in the ventral ectodermal cells of each parasegment in the embryo, though transcript is still found in other cells where wg expression is independent of hh function. The phenotype stays the same even if Hh is overexpressed with HS-hh. (Ingham, 1993)
Hedgehog
- Overexpression of hh in embryos with a HS-hh construct wg is ectopically expressed anterior to each normal wg domain, but more anterior cells don't express wg. ptc, however, is expressed in all cells except engrailed expressing cells. (Ingham, 1993)
- In en-Gal4/UAS-wg; hh^- embryos Winglessis spreads posterior to the engrailed domain as if a barrier had been lifted or Wingless movement enhanced (Figure 5B). Wingless protein distribution is symmetrical, and this is reflected in the cuticle pattern: in contrast to en-Gal4/UAS-wg embryos, en-Gal4/UAS-wg; hh^- embryos lack rows 2–4 and, instead, have an extra expanse of naked cuticle (Figure 5C). At the positions where rows 5 and 6 normally form, lies a thin stripe of small denticles. Naked cuticle is specified equally in the anterior and posterior directions, as shown by marking the winglessexpressing cells with GFP (Figure 5C). Thus, in the absence of hedgehog, wingless action is symmetric. (Sanson, 1999)
Hedgehog signaling
- The posterior barrier to Wingless protein in the embryo requires Hedgehog signaling (Sanson, 1999)
- Excess hedgehog signaling reduces the range of Wingless (Sanson, 1999)
Rhomboid
- rhomboid expression is abolished by continuous and uniform expression of Wingless (using the transgene combination arm-Gal4/UAS-wg). Also delayed addition of Wingless up to mid-stage 11 with UAS-wingless^ts also wipes out rhomboid expression. Later ectopic expression, induced at late stage 11, inhibits rhomboid transcription only in the midventral region (Fig 3C), and if sibling embryos are left to develop, they make ectopic naked cuticle in the same region (Figure 3D). Therefore, Wingless can repress rhomboid transcription in the same time window as it specifies naked cuticle. Wingless is not only sufficient for rhomboid repression, it is also necessary since wingless null mutants have an additional rhomboid stripe in each abdominal segment (Figure 3B). The position of these extra stripes relative to landmarks in the CNS (data not shown) suggests that they form at the anterior of the domain of extinct engrailed expression, where wingless would normally be expressed. Thus, in the wild type, the presence of Wingless at the anterior of each engrailed stripe keeps rhomboid expression off there (see Figure 3E).(Sanson, 1999)
- in en-Gal4/UAS-wg larvae, rhomboid expression is is unchanged (Fig 4B), indicating that the wingless pathway is not operative in the cells immediately posterior to the wingless misexpressing cells. Thus, it appears that Wingless cannot cross the posterior edge of the engrailed domain. This was verified by looking directly at the distribution of Wingless protein in en-Gal4/UAS-wg embryos. In these embryos, Wingless is present within the domain of wing-less misexpression, as expected. However, it is not detectable posterior to the engrailed-expressing cells (Figures 4C and 4D). Therefore a barrier to Wingless protein movement exists at the presumptive segment boundary. (Sanson, 1999)
shavenbaby
- shavenbaby is repressed in response to wingless signaling (Payre, 1999)
Col and En expression is up-regulated in pka-C1 and wg double mutants both at a distance from and close to the DV boundary (Fig 4A & 4C), however, Col (but not En) up-regulation is never observed in the prospective wing margin (Fig 4A) (Glise, 2002)
- This indicates that Wg is responsible for the repression at a distance from the DV boundary but not at the wing margin itself (Glise, 2002)
- Ectopic expression of Wg driven in the wing pouch by 71B-GAL4 results in a decrease in Col expression (Fig 5) (Glise, 2002)
- Ectopic expression of Wg, Dsh, or a dominant-active form of Arm (Arm^S10) in a fu¹ mutant driven in the wing pouch by 71B-GAL4 results in a decrease in Col expression (Fig 5) (Glise, 2002)
In vn null mutants, the initiation of wg expression is normal and the expression of its target gene optomotor-blind (omb) (Grimm and Pflugfelder 1996; (Wang, 2000: Fig 1)
Cubitus interruptus
- Ci-75 is needed to repress wg latter in embryo development
  - ci single mutant and ci hh double mutant embryos are close to wild-type size and show considerable naked cuticle ventrally, ci wg double mutants are small and exhibit a 'lawn-of-denticle' phenotype (Methot, 2001)
all epidermal cells are able to respond to Wg at stage 11 (Sanson, 1999)

{Physical interactions}

{Regulation}

{Structure}

In second instar wild-type wing discs, wg is expressed distally in a wedge of anterior ventral cells (Couso et al. 1993; Williams et al. 1993; Ng et al. 1996)
Wingless is distributed asymmetricly in the embryo. Wingless-containg vesicles can be seen at the site of endogenous wingless expression and anteriorly. In contrast, few vesicles can be found in the engrailed domain. (Sanson, 1999)

Wingless movement is restricted posteriorly in the embryo.
- The first restriction occurs within the engrailed domain and is unlikely to be under hedgehog control, since engrailed cells are not thought to respond to Hedgehog (Basler and Struhl, 1994). Rather, engrailed could implement this restriction by controlling a gene involved in Wingless transport, sequestration, or stability.
- The barrier at the posterior of the engrailed domain requires hedgehog signaling. Wingless produced ectopically in the engrailed domain of hedgehog mutants is allowed to invade posteriorly located cells (Figure 5B) and induce naked cuticle there (Figure 5C). The same effects is seen in cubitus interruptus mutants indicating that the hedgehog signaling pathway is involved. The role of the hedgehog pathway is confirmed by “gain-of-function” experiments (see Sanson, 1999). Loss of patched results in overactivation of the hedgehog pathway (Ingham, 1993) and so does excessive hedgehog expression. As shown in Figure 6, both situations reduce the range of Wingless in the anterior direction as if the spread of the protein were reduced. Sanson, 1999 presume that, in the wild type, a downstream Hedgehog target is upregulated at the posterior of each engrailed/ hedgehog stripe and this would lead to Wingless destabilization or a block to transport there. (Sanson, 1999)

{Related to}

Wg mutants have a complete loss of all wing structures replaced by a tiny duplication of notal structures (Sharma, 1976; Morata, 1978)
In wg mutants there is a dramatic and early expansion of vn expression to include distal cells (Wang, 2000: Fig 1I), presaging the development of these cells as an extra notum.

ectopic expression of wg at the correct time leads to the ectopic induction of wing structures in the notum.
Ectopic expression of Wg driven in the wing pouch by 71B-GAL4 results in a decrease in Col expression (Fig 5) (Glise, 2002)
Ectopic expression of Wg, Dsh, or a dominant-active form of Arm (Arm^S10) in a fu¹ mutant driven in the wing pouch by 71B-GAL4 results in a decrease in Col expression (Fig 5) (Glise, 2002)
Uniform wingless expression initiated at mid-stage 11 (6.5 hr AEL), using a UAS-wingless^ts driven by arm-Gal4, is sufficient to force most cells to make naked cuticle (Fig 1D) (Sanson, 1999)
misexpressed wingless using a en-Gal4/UAS-wg caused a loss of row 1 denticles (Fig 4A) (Sanson, 1999)
In en-Gal4/UAS-wg; hh^- embryos Winglessis spreads posterior to the engrailed domain as if a barrier had been lifted or Wingless movement enhanced (Figure 5B). Wingless protein distribution is symmetrical, and this is reflected in the cuticle pattern: in contrast to en-Gal4/UAS-wg embryos, en-Gal4/UAS-wg; hh^- embryos lack rows 2–4 and, instead, have an extra expanse of naked cuticle (Figure 5C). At the positions where rows 5 and 6 normally form, lies a thin stripe of small denticles. Naked cuticle is specified equally in the anterior and posterior directions, as shown by marking the winglessexpressing cells with GFP (Figure 5C). Thus, in the absence of hedgehog, wingless action is symmetric. (Sanson, 1999)
- This effect is due to Hedgehog signaling since the cuticle phenotype of en-Gal4/UAS-wg; ci^- embryos is identical to that of en-Gal4/UAS-wg; hh^- embryos (Figure 5G). This requirement is dose sensitive, since in hedgehog or cubitus interruptus heterozygotes, Wingless produced in the engrailed domain generates occasional breaches of naked cuticle in the denticle belts (Figures 5H and 5K ). (Sanson, 1999)

{Reagents}