Fig. 1.

Control of wing growth by Dpp and Wg. (A–E) Morphology, morphogen sources, and proliferative growth of the wing primordium. (A) The wing derives from a central population of cells within the wing imaginal disc that express the wing selector gene vestigial (vg), surrounded by concentric populations of pre-wing, hinge, and notum (body wall) cells as indicated (Vg protein, red; DNA, here and in the remaining figures counterstained with Hoeschst, blue). (B–E) vg expression is controlled by a cis-acting QE, which is activated in wing cells by Dpp and Wg emanating from source cells along the A/P and D/V compartment boundaries (magenta and blue, respectively, in B and E; QE activity is monitored by expression of a 5XQE.DsRed reporter gene, VgQE, red in C and D). vg is also controlled by a “boundary” enhancer (BE) activated by Notch signaling along the entire D/V boundary and in prevein territories in the mature wing, particularly in the vicinity of the A/P boundary (as monitored by a BE.lacZ reporter gene, vgBE, green in C). Notch signaling represses the QE, as visualized by the absence of 5XQE.DsRed expression along the D/V boundary and its partial suppression along the A/P boundary in D; hence, Vg expression in the entire wing disc (A) reflects the complimentary contributions of BE- and QE-dependent vg transcription. Growth of the wing proper is monitored by the near-uniform proliferative expansion of the population of QE-dependent Vg-expressing cells (monitored by EdU incorporation during S phase in D, turquoise). (F and G) Two distinct modes of growth that terminate when the wing reaches full size are diagrammed in the expanded region of the wing edge boxed in yellow in E (see ref. 21). In the first mode (G, right side), pre-wing cells encircling the wing are induced to grow (green), initiate QE-dependent Vg expression (orange), and enter the wing by the combined inputs of Dpp and Wg emanating from A/P and D/V border cells, as well as a membrane-bound, Vg-dependent FF signal, the protocadherin Fat. Fat operates via the Warts/Hippo tumor suppressor pathway to facilitate nuclear access of the transcriptional activator Yki, which acts directly on the QE enhancer. In the second mode (F, left side), Vg substitutes for Yki to autoregulate its own expression (red) and also programs wing cells to grow, both in response to Dpp and Wg (turquoise). Thus, as depicted at the bottom, the progressive outward spreads of Dpp and Wg (Morphogen) propel a wave front (arrow) of Yki activity, pre-wing growth, and recruitment that propagates away from the wing center, with the newly recruited wing cells serving as new sources of FF signal. Behind the front, Dpp and Wg retain cells within the wing proper (by fueling the autoregulation of Vg) and sustain their continuing growth, further expanding wing size.