DER signaling restricts the boundaries of the wing field during Drosophila development

Abstract

Arthropod and vertebrate limbs develop from secondary embryonic fields. In insects, the wing imaginal disk is subdivided early in development into the wing and notum subfields. The activity of the Wingless protein is fundamental for this subdivision and seems to be the first element of the hierarchy of regulatory genes promoting wing formation. Drosophila epidermal growth factor receptor (DER) signaling has many functions in fly development. Here we show that antagonizing DER signaling during the second larval instar leads to notum to wing transformations and wing mirror-image duplications. DER signaling is necessary for confining the wing subregion in the developing wing disk and for the specification of posterior identity. To do so, DER signaling acts by restricting the expression of Wingless to the dorsal-posterior quadrant of wing discs, suppressing wing-organizing activities, and by cooperating in the maintenance of Engrailed expression in posterior compartment cells. D uring development, cellular identities are specified within initially undifferentiated fields of cells (1). This specification is achieved by the progressive determination of cells by particular regulators that increasingly restrict their developmental potential. The growth and patterning of the wing disk of Drosophila is directed from organization centers that are created by the juxtaposition of anterior and posterior (A͞P) and dorsal and ventral (D͞V) compartments (2-4) generated during the development of the disk. How these axial attributes participate in the specification of both distal (wing) and proximal (notum, hinge) subfields (5) is not well established.Drosophila epidermal growth factor receptor (DER) signaling has been implicated in the control of cell size, cell proliferation, and the allocation of vein cell fates in the wing disk (reviewed in ref. 6). The expression of vein (vn), a gene coding for a DER ligand, is restricted to a posterior and dorsal domain in second instar wing discs (7, 8) (see Fig. 1H). Hypomorphic alleles of vn show pattern duplications of anterior structures replacing posterior territories in the wing disk (7). Similar phenotypes have been found in some allelic combinations of pointed, a gene that codes for a transcription factor putatively under DER control (9). These findings suggest that the activation of the DER signaling cascade could be involved in assuring the specification of posterior cells in the wing. On the other hand, the specification of the wing field relies on the expression of wingless (wg) at second larval instar stages (10, 11). The ectopic expression of Wg at this stage can induce wing tissue in notum territories (10). However, the ability of wg to activate wing specification is spatially restricted to cells at central positions of the disk, which suggests that a second activity limits the competence of cells to respond to wg and restricts the size and the position of the wing field (10). Here we show that DER signaling is involved in the maintenance of Engrailed (En) expression in poste...

Competition among gene regulatory networks imposes order within the eye-antennal disc of Drosophila

“…Our identification of a potential phenocritical period for the eye-head capsule choice might be relevant to other tissue fate decisions as well. For instance, the critical window for the wing-notum decision has been mapped to the late second instar (Baonza et al, 2000), and the induction of ectopic eyes (non-retinal to retinal transformation) appears in most instances to be synchronous with the specification of the normal eye (Salzer and Kumar, 2010). Together, these results suggest that a potential global developmental window for imaginal disc fate decisions exists and is centered around the late second larval/early third instar stage.…”

Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila

“…4J). Wg and DER function cooperatively but antagonistically through complimentary expression to pattern developing tissues (43,44). Therefore, simultaneous misexpression of both Wg and vn may abrogate function of both signaling pathways.…”

KSR and CNK: two scaffolds regulating RAS-mediated RAF activation

“…As ksr alleles, cnk mutations suppressed RTK or RAS gain-of-function activity, but had no effect on a constitutively active RAF, and thus suggested that cnk is also required upstream of RAF (Therrien et al, 1998). Functional analysis of cnk revealed that its activity is not restricted to eye development, but is operating in other RTK-mediated developmental events affecting cell proliferation/survival, differentiation and migration, and thereby implied a general role for CNK in Drosophila RTK signaling (Therrien et al, 1998;Baonza et al, 2000;Cabernard and Affolter, 2005). Initial characterization of the CNK protein revealed its ability to interact with RAF, which suggested that it directly regulates RAF (Therrien et al, 1998).…”