Reviews: (Klein; 2002)

• Vein formation: rho and Dl are essential components of EGF- and Notch-mediated signalling, respectively, both of which processes are required for resolution of vein and intervein cell-fate determination (Sturtevant, 1995). The expression of rho and Dl in individual vein primordia is presaged by the expression of vein-specific vein-promoting genes, each of which is necessary for the specification of a particular vein. These vein-specific vein-promoting genes include kni, which is required for vein 2 (Sturtevant, 1995; Lunde et al., 1998), ara/caup, a pair of partially redundant genes of the iroquois complex that are required for the odd-numbered veins (veins 1, 3 and 5; Gomez- Skarmeta and Modolell, 1996; Gomez-Skarmeta et al., 1996) and ab, which is required for vein 5 (Sturtevant, 1995). In the case of vein 2, expression of kni is induced just outside the anterior boundary of the expression domain of sal (a Dpp target) by some unknown signal from sal expressing cells (Lunde et al., 1998). For the other three predominant longitudinal veins, it is not clear how the global patterning elicited by Hh- and Dpp signalling results in the positioning of the vein primordia within the wing disc.[taken from (Mohler, 2000)]
• "The wing in Drosophila develops from one of the imaginal discs from which most of the adult body is assembled. Imaginal discs are monocellular epithelial layers that consist of undifferentiated, proliferating cells. The wing imaginal disc comprises ~20 cells when it is formed during embryonic development. These cells proliferate during the three larval stages to generate a disc of ~75,000 cells in the late third instar (~96h after hatching). The disc is basically a single cell layered epithelium, thus pattern formation occurs in a two-dimensional layer. This presents a problem, one also shared by a painter: incorporating the third dimension in a two dimensional sheet. It is solved by organizing the wing primordium in a concentric way with the distal structures (wing blade and margin) in the center and the proximal structures (hinge) at the periphery (Figure 1)." (Klein; 2002)
• "By the late third instar, the wing primordium is established and one can identify its major elements, hinge, blade and margin, with the help of appropriate molecular markers (see Figure 1). However, the processes leading to its formation start at the beginning of the third larval instar (~48h after hatching) and are controlled by two major patterning centers, that are established at the boundaries of the dorsoventral (D-V) and anteroposterior (A-P) compartments." (Klein; 2002)
• "Several genetic screens have identified important genes controlling wing development: chief among them engrailed (en), apterous (ap), vestigial (vg), and the genes that play a role in the Notch (N) Decapentaplegic (Dpp), Wingless (Wg), Hedgehog (Hh), and epidermal growth factor receptor (EGF-R) signaling pathways." (Klein; 2002)
• Studies of imaginal disc formation in the embryo showed that the wing and leg discs have a common precursor which later separate as a result of the dorsal segregation of the wing disc [11,12]. This common precursor is established at the A-P boundary within the mesothoraxic segment and consists of En-expressing and non-expressing cells [12]. Therefore, it seems that the A-P boundary is inherited from the embryo and is maintained in the wing and leg discs through later stages. The common disc precursor also includes Wg-expressing cells at the ventro-anterior position [12], but because the wing disc arises from the dorsal part of the common precursor, the wing disc does not inherit wg-expressing cells and therefore initially has no obvious D-V boundary.
• Formation of posterior L4 vein requires activity of vein (vn), which encodes a diffusible neuregulin-like protein, one of the known EGFR ligands and activates the EGF pathway (Schnepp et al., 1996; Simcox et al., 1996).
• specification of L3 vein per se does not depend on col, but on activity of the homeobox-containing genes araucan (ara) and caupolican (cau) from the iroquois complex (iro-C) (Gomez-Skarmeta et al., 1996; Gomez-Skarmeta and Modolell, 1996).
• Formation of L4 vein depends upon appropriate regulation of both Dpp and EGF signalling in the AP organiser. (Crozatier, 2002)
• Positioning L3 vein: crosstalk between Hh and Dpp signalling via col and iro regulation
  • It has previously been proposed that Hh does directly control
    the position of L3 vein, although the molecular mechanisms of
    this control were not firmly established (Mullor et al., 1997;
    Stigini and Cohen, 1997). In both col (Nestoras et al., 1997)
    (this paper) and mtv mutant clones (Tanimoto et al., 2000), the
    position of L3 vein is shifted posteriorwards. That both col and mtv control the position of L3 vein suggested that this position
    is defined by Hh signalling through the modulation of Dpp
    signalling. It has previously been established that iro was
    required for rho activation in the L3 primordium and formation
    of L3 vein (Gomez-Skarmeta et al., 1996; Gomez-Skarmeta
    and Modolell, 1996). iro is activated by both Dpp and Hh
    signalling and its anterior border of expression is under control
    of sal/salr, a target of Dpp (De Celis and Barrio, 2000). We
    show that the patterns of col, iro and rho expression are
    intimately connected. We observed both an increased number
    of cells expressing rho and a posterior shift of the anterior
    border of iro expression in col1 mutant discs. We interpret this
    posterior shift as reflecting a modified range of Dpp signalling
    relayed, at least in part, by sal/salr activity. The increased
    number of rho-expressing cells, for its part, indicated that Col
    is able to antagonise rho activation by iro in cells, which
    express both iro and Col. This correlates well with the wing
    phenotype – anteriorwards shift of the L3 vein, together with
    gaps in its distal region – which results from anterior extension
    of Col expression, in UAS-Col/dpp-Gal4 wing discs (Mohler
    et al., 2000) (M. C., unpublished). The distal gaps could reflect
    the complete absence of rho expression close to the DV border,
    because of the complete overlap between col and iro expression
    where iro expression is narrower. From col loss- and gain-of
    function experiments, we therefore conclude that the
    primordium of L3 vein corresponds to cells that express iro but
    not col (Fig. 4I). Col thus appears to play a dual role in defining
    the position and width of L3 vein: activating BS and repressing
    EGFR in the wing AP organiser cells, endows these cells with
    an intervein fate, while attenuating Dpp signalling indirectly
    positions the anterior limit of iro expression domain, and L3
    vein competence anterior to the AP organiser (Fig. 6). (Crozatier, 2002)
• Formation of L4 vein depends upon appropriate regulation of both Dpp and EGF signalling in the AP organiser
  • We have shown that Col regulates vn transcription in the AP
    organiser. This expression of vn is required for formation of L4
    vein (Garcia-Bellido et al., 1994; Schnepp et al., 1996; Simcox
    et al., 1996). The loss of this vein in col1 mutants could not,
    however, be rescued by expressing high level of Vn in the AP
    organiser, suggesting that a second signal dependent upon Col
    was also required. The specific loss of L4 vein was previously
    observed in conditions of reduced levels of Dpp signalling
    caused by ubiquitous expression of either Tkv or TkvDN
    (Haerry et al., 1998). Together with this, the col1 wing
    phenotype and Col requirement for downregulation of Dpp
    signalling in the AP organiser suggested a role of Dpp
    signalling in formation of L4 vein. Indeed, expressing a
    dominant-negative form of Tkv (TkvDN) in the AP organiser
    resulted in L4 loss. At first sight, it may appear contradictory
    that either upregulation (in col mutants) or downregulation (by
    expressing TkvDN) of Dpp signalling in the AP organiser leads
    to the preferential loss of posterior L4 vein. In both cases,
    however, there is increased sequestering of Dpp in the AP
    organiser, which limits its range of diffusion and signalling in
    posterior cells (Haerry et al., 1998; Lecuit and Cohen, 1998).
    Therefore attenuation of Dpp signalling in the AP organiser
    and increased signalling in posterior flanking cells (Tanimoto
    et al., 2000) appears to be required in addition to Vn activity
    for formation of L4 vein. By modulating Dpp signalling and vn transcription in cells receiving high doses of Hh, Col thus
    links Hh short-range activity to both positioning of the anterior
    L3 vein and formation of the posterior L4 vein. (Crozatier, 2002)