Control of Drosophila wing size by morphogen range and hormonal gating

Abstract

The stereotyped dimensions of animal bodies and their component parts result from tight constraints on growth. Yet, the mechanisms that stop growth when organs reach the right size are unknown. Growth of the Drosophila wing—a classic paradigm—is governed by two morphogens, Decapentaplegic (Dpp, a BMP) and Wingless (Wg, a Wnt). Wing growth during larval life ceases when the primordium attains full size, concomitant with the larval-to-pupal molt orchestrated by the steroid hormone ecdysone. Here, we block the molt by genetically dampening ecdysone production, creating an experimental paradigm in which the wing stops growing at the correct size while the larva continues to feed and gain body mass. Under these conditions, we show that wing growth is limited by the ranges of Dpp and Wg, and by ecdysone, which regulates the cellular response to their signaling activities. Further, we present evidence that growth terminates because of the loss of two distinct modes of morphogen action: 1) maintenance of growth within the wing proper and 2) induced growth of surrounding “pre-wing” cells and their recruitment into the wing. Our results provide a precedent for the control of organ size by morphogen range and the hormonal gating of morphogen action.

A unified mechanism for the control of Drosophila wing growth by the morphogens Decapentaplegic and Wingless

“…Hence, as previously proposed [ 64 – 66 ; 111 ], Dpp and Wg act instructively to control wing growth as a function of morphogen range. In agreement, wing growth during larval life appears to cease when Dpp and Wg reach their maximum ranges, but can be reinitiated by manipulations that extend their ranges [ 171 ].…”

Ecdysone coordinates plastic growth with robust pattern in the developing wing

“…For example, insulin/TOR signalling regulates the activity of Yorkie, a downstream effector of patterning morphogens, including Wingless and Dpp, that controls the rate of cell division [79]. Similarly, reducing ecdysone signalling in the wing reduces the expression of Wingless and reduces Dpp signalling, measured by the levels of phosphorylated Mothers against Dpp expression [56, 58, 59, 80]. Further, ecdysone acts to gate when cells of the wing can respond to these morphogens, limiting the extent of wing growth [80].…”

“…Similarly, reducing ecdysone signalling in the wing reduces the expression of Wingless and reduces Dpp signalling, measured by the levels of phosphorylated Mothers against Dpp expression [56, 58, 59, 80]. Further, ecdysone acts to gate when cells of the wing can respond to these morphogens, limiting the extent of wing growth [80]. Taken together, the signalling pathways that regulate organ growth in response to environmental conditions interact in complex ways with those that regulate organ-autonomous growth suggesting that these two growth regulating mechanisms are not as independent as previously thought [6].…”

Interplay between cell proliferation and recruitment controls the duration of growth and final size of the Drosophila wing

“…Evidence suggests that chemical gradients (morphogens), nutrition, hormones, and mechanical interactions contribute to extrinsic and intrinsic growth, but how all these signals are integrated to result in a wing of a specific size and shape is little understood [9,10,11,12,13]. While extrinsic factors determine the ultimate size of the wing, transplantation experiments of wing discs into the abdomen of an adult fly or experiments in which pupation is halted and the duration of larval development is increased, show that discs are able to stop growing when a particular size is reached [14,15,16]. Moreover, the fact that wing discs stop growing at the 'right' size even when cell proliferation, cell sizes, or cell numbers are perturbed suggest that there are intrinsic mechanisms that robustly control the final size of the disc [17,18].…”