Morphogen gradient scaling by recycling of intracellular Dpp

Maria Romanova-Michaelides (), Zena Hadjivasiliou, Daniel Aguilar-Hidalgo, Dimitris Basagiannis, Carole Seum, Marine Dubois, Frank Jülicher () and Marcos Gonzalez-Gaitan ()
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Maria Romanova-Michaelides: University of Geneva
Zena Hadjivasiliou: University of Geneva
Daniel Aguilar-Hidalgo: University of Geneva
Dimitris Basagiannis: University of Geneva
Carole Seum: University of Geneva
Marine Dubois: University of Geneva
Frank Jülicher: Max Planck Institute for the Physics of Complex Systems
Marcos Gonzalez-Gaitan: University of Geneva

Nature, 2022, vol. 602, issue 7896, 287-293

Abstract: Abstract Morphogen gradients are fundamental to establish morphological patterns in developing tissues1. During development, gradients scale to remain proportional to the size of growing organs2,3. Scaling is a universal gear that adjusts patterns to size in living organisms3–8, but its mechanisms remain unclear. Here, focusing on the Decapentaplegic (Dpp) gradient in the Drosophila wing disc, we uncover a cell biological basis behind scaling. From small to large discs, scaling of the Dpp gradient is achieved by increasing the contribution of the internalized Dpp molecules to Dpp transport: to expand the gradient, endocytosed molecules are re-exocytosed to spread extracellularly. To regulate the contribution of endocytosed Dpp to the spreading extracellular pool during tissue growth, it is the Dpp binding rates that are progressively modulated by the extracellular factor Pentagone, which drives scaling. Thus, for some morphogens, evolution may act on endocytic trafficking to regulate the range of the gradient and its scaling, which could allow the adaptation of shape and pattern to different sizes of organs in different species.

Date: 2022
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DOI: 10.1038/s41586-021-04346-w

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