Understanding morphogenetic growth control — lessons from flies

Abstract

Morphogens are secreted signalling molecules that control the patterning and growth of developing organs. How morphogens regulate patterning is fairly well understood; however, how they control growth is less clear. Four principal models have been proposed to explain how the morphogenetic protein Decapentaplegic (DPP) controls the growth of the wing imaginal disc in the fly. Recent studies in this model system have provided a wealth of experimental data on growth and DPP gradient properties, as well as on the interactions of DPP with other signalling pathways. These findings have allowed a more precise formulation and evaluation of morphogenetic growth models. The insights into growth control by the DPP gradient will also be useful for understanding other morphogenetic growth systems.

Dpp signaling inhibits proliferation in the Drosophila wing by Omb-dependent regional control of bantam

“…A number of models have been proposed to interpret how Dpp controls proliferation in the wing disc (Aegerter-Wilmsen et al, 2007;Day and Lawrence, 2000;Garcia-Bellido and Merriam, 1971;González-Gaitán et al, 1994;Hufnagel et al, 2007;Shraiman, 2005;Wartlick and González-Gaitán, 2011;Wartlick et al, 2011a). Recent observations argue that at least the spatial gradient of Dpp (and Wingless) is not essential for proliferation regulation in the wing disc (Baena-Lopez et al, 2009;Schwank et al, 2008).…”

“…The control of organ growth by extrinsic and intrinsic factors is a fundamental aspect of animal development that remains poorly understood (Baena-Lopez et al, 2012;Day and Lawrence, 2000;Johnston and Gallant, 2002;Schwank and Basler, 2010;Wartlick et al, 2011a). The Drosophila wing imaginal disc is a popular model for testing hypotheses on cell proliferation control.…”

Modulation of junction tension by tumor-suppressors and proto-oncogenes regulates cell-cell contacts

“…The analyses of these functions have led to important advances in our understanding of tissue development and homeostasis as well as pathologies, including tumorigenesis (for reviews, see Zhao et al, 2011;Patel and Edgar, 2014;Baillon and Basler, 2014). In Drosophila, analysis of the sizes and shapes of somatic clones affecting tumor suppressor and proto-oncogene activities is instrumental to understanding their contribution in tissue morphogenesis, organization and homeostasis (Resino et al, 2002;Baena-Lopez et al, 2005;Mao et al, 2011;Wartlick et al, 2011;Kuchen et al, 2012;Worley et al, 2013;Restrepo et al, 2014;Heemskerk et al, 2014). Accordingly, somatic mutant clones are essential for unveiling how tumor suppressor and proto-oncogene activities modulate tissue proliferation, growth, cell-cell interactions and cell competition (for a review, see Wagstaff et al, 2013).…”

Adaptation of the length scale and amplitude of the Bicoid gradient profile to achieve robust patterning in abnormally large Drosophila melanogaster embryos

“…This is reflective of the robust nature of the developmental process in the face of inevitable variations at all levels, ranging from molecular to organismal and environmental levels (Patel and Lall, 2002;Flatt, 2005;Martinez Arias and Hayward, 2006;Hendrikse et al, 2007;Lander, 2007;Lott et al, 2007). A full, mechanistic understanding of scaling requires knowledge about two distinct aspects of development: specification of scaled patterns and coordinated tissue growth (Su and O'Farrell, 1998;Day and Lawrence, 2000;Crickmore and Mann, 2008;BenZvi et al, 2011;Wartlick et al, 2011;Yang and Xu, 2011;BaenaLopez et al, 2012). Recent quantitative studies have uncovered insights into scaled patterning specification in Drosophila (Houchmandzadeh et al, 2002;Gregor et al, 2005;He et al, 2008;Manu et al, 2009;Cheung et al, 2011).…”