Dynamics of Dpp Signaling and Proliferation Control

Abstract

Morphogens, such as Decapentaplegic (Dpp) in the fly imaginal discs, form graded concentration profiles that control patterning and growth of developing organs. In the imaginal discs, proliferative growth is homogeneous in space, posing the conundrum of how morphogen concentration gradients could control position-independent growth. To understand the mechanism of proliferation control by the Dpp gradient, we quantified Dpp concentration and signaling levels during wing disc growth. Both Dpp concentration and signaling gradients scale with tissue size during development. On average, cells divide when Dpp signaling levels have increased by 50%. Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates.

Dynamic scaling of morphogen gradients on growing domains

“…1d). Accordingly, the Dpp concentration appears to increase with time for every single cell 15 (Fig. 1c).…”

“…This model, however, does not apply to the Decapentaplegic (Dpp) gradient in the Drosophila wing and haltere imaginal discs, because measurements show that the gradients indeed widen with the expanding domain 15 . In parallel, however, also the maximal value of the gradients increases in the Drosophila wing and haltere imaginal discs, as well as in the early Drosophila embryo 9,14,15,22 ( Fig. 1c), such that the measured gradients fall on the same curve (that is, scale) only when rescaled both relative to their maximal value and relative to the length of the domain (Fig.…”

“…x / L(t) c(t) / c (c) Both the height, c 0 , and the length of the measured 15 Dpp gradient (equation (1)) increase on the growing wing imaginal disc of length L(t).…”

“…1b). Different models have been proposed to explain the scaling of morphogen gradients in the various systems where scaling has been analysed [9][10][11][12][13][14][15][16][17] . However, these models have remained controversial because of conflicting experimental observations 16,[18][19][20][21] .…”

Size and shape—integration of morphometrics, mathematical modelling, developmental and evolutionary biology

“…Population level variation in teeth morphology and tooth type differences in seals have been translated into mathematical models to disentangle the stages of development and the respective signaling changes responsible for the observed shape changes (Salazar-Ciudad and Jernvall 2010). In Drosophila, computational models exist that explain patterning of the dorsal head region (Aguilar-Hidalgo et al 2013) and growth control in the wing imaginal disc (Wartlick et al 2011). …”