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Control of growth and patterning of the Drosophila wing imaginal disc by EGFR-mediated signaling

Department of Genetics and Development, Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA

View larger version (91K): [in a new window]   Fig. 1. Vn-expressing clones in vn mutant discs. (A-D) vn– discs containing clones ectopically expressing Vn, monitored for the expression of Ap (red in middle panels) and mirr-lacZ (red in right panels). Clones were induced during the first instar and are marked by absence of GFP expression (green). (A) vn– disc containing multiple Vn-expressing clones. The size and shape of the disc are close to normal, as are the patterns of Ap and mirr-lacZ expression. The inset shows a vn mutant disc at the same magnification. (B) vn– disc containing a single dorsolaterally positioned Vn-expressing clone (arrow). The clone is associated with a long-range, non-autonomous rescue of Ap expression, but only a short-range rescue of mirr-lacZ expression in a restricted lateral region of the presumptive wing hinge where it is normally expressed. The notum primordium is absent. (C) vn– disc containing a laterally positioned clone of Vn-expressing cells (arrow). Some rescue of growth is observed, which is associated with the induction of a non-contiguous patch of Ap-expressing cells that form an abnormally small D compartment. As in (B), mirr-lacZ expression is rescued at short-range in a lateral region of the wing hinge and the notum primordium is absent. A small Vn-expressing clone is also present in the extreme dorsoproximal region of the disc. (D) vn– disc containing a single large clone within prospective notal territory. Note that both the size and shape of the disc appear almost normal, as do the patterns of Ap and mirr-lacZ expression.

View larger version (74K): [in a new window]   Fig. 2. Ectopic Rho expression in wild-type and vn mutant discs. (A-E) Wild-type (A-C) and vn– (D,E) discs containing clones that ectopically express Rho, monitored for the expression of Ap (B,D; red in middle panels), ap-lacZ (C; red), mirr-lacZ (B,D,E; red in middle or right panels), vgQ-lacZ (A; red), Vg (A; blue) and Wg (C; blue). The clones were induced during the first instar and are marked by absence of GFP expression (green). (A) Duplicated wing blade primordium (outlined in the right panel; the extra primordium is outlined in yellow) caused by a ventrally situated clone of Rho-expressing cells (arrowhead) which we infer has induced the formation of an ectopic D compartment. Note that expression of the vg gene (visualized by Vg protein expression, blue) is normally expressed along the DV compartment boundary (asterisks) in response to Notch signaling and in the remainder of the wing blade primordium in response to Wg emanating from the boundary. Expression of the vgQ-lacZ gene (red) depends on the vg ‘quadrant’ enhancer, which is activated by Wg signaling, but blocked by Notch signaling, thus allowing the ectopic DV boundary that forms within the duplicated wing blade primordium to be visualized (yellow asterisk). (B) Ectopic expression of mirr-lacZ and expansion of Ap expression caused by a dorsolateral clone of Rho-expressing cells. Note that ectopic mirr-lacZ is closely associated with the clone, outlined in white, in contrast to boundary of expression of Ap expression, which extends many cell diameters further ventrally. (C) Expansion of ap-lacZ expression caused by two dorsally situated clones of Rho-expressing cells located within the dorsal compartment. Wg is expressed in cells flanking the apON-apOFF interface, indicating that the boundary has organizer activity. (D) Partial rescue of growth and patterning of a vn mutant disc by clones ectopically expressing Rho. The boundaries of mirr-lacZ expression are located close to the clone, whereas those of Ap expression are located further away. (E) Extensive rescue of a vn– mutant disc by a single dorsally situated clone of Rho-expressing cells.

View larger version (45K): [in a new window]   Fig. 3. Ras activity inhibits the organizing capacity of the DV compartment boundary. (A-E) vn– (A,B,E) and wild-type (C,D) discs containing clones ectopically expressing either RasV12 (A,C,D), Rho (B) or Ap (E) monitored for the expression of Ap (red in A,C,E), ap-lacZ (red in B,D), Wg (blue in B), wg-lacZ (blue in C) and Vg (blue in D). Clones were induced during the first instar and are marked by presence (A,C,D) or absence (B,E) of GFP expression (green). Clones in B appear in red. Overlap of red and green signals appear in yellow (B-D). (A) vn mutant disc containing a RasV12-expressing clone that induces ap expression autonomously, but fails to exert a non-autonomous effect on proliferation of neighboring vn mutant cells. The inset shows a vn mutant disc at the same magnification. (B) Rho-expressing clones (arrows) that exert a non-autonomous effect on both ap-lacZ expression and proliferation of vn mutant cells. The apON-apOFF interface is associated with Wg expression. Note that the disc is shown at 1.3x the magnification used in A. (C) Wild-type disc containing a RasV12-expressing clone that autonomously expresses Ap, but does not induce wg-lacZ expression along the clone border. (D) Clones of RasV12-expressing cells in a wild-type disc autonomously induce ap-lacZ and repress Vg expression. (E) vn mutant disc containing an Ap-expressing clone that non-autonomously rescues the proliferation of the wing blade primordium. The disc is shown at the same magnification as the disc in A.

View larger version (34K): [in a new window]   Fig. 4. Control of wing disc development by EGFR signaling. (I) Early during larval development, high levels of EGFR signaling activate ap (hatched) and the Iro-C (yellow) genes in overlapping domains within the dorsoproximal region of the wing disc. (II) During subsequent development, Iro-C expression depends on continuous EGFR input. Hence, Iro-C expression remains confined to the area of high EGFR signaling (yellow), segregating the disc into distinct notum (yellow) and wing (white) primordia. By contrast, ap expression, once activated, becomes heritable, segregating the disc into D (apON, hatched) and V (apOFF, unhatched) compartments. Hence, as the disc grows, ventrally situated cells within the D compartment continue to express ap, even after they move out of the range of high EGFR signaling. The shift of the DV boundary into a region of low EGFR signaling appears essential to allow D and V compartment cells to interact to initiate a positive feedback loop of reciprocal Notch signaling that drives the expression of Wg, Vg and other ‘boundary’ genes (green). (III) The products of these genes then organize the subsequent growth and differentiation of the prospective wing blade (including the long-range induction of Vg, which defines the wing blade primordium, blue), and the prospective wing hinge (defined by the absence of Vg and Iro-C expression, white).