4.8 Article

Morphogen gradient scaling by recycling of intracellular Dpp

期刊

NATURE
卷 602, 期 7896, 页码 287-+

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NATURE PORTFOLIO
DOI: 10.1038/s41586-021-04346-w

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资金

  1. HFSP long-term fellowship
  2. DIP of the Canton of Geneva
  3. SNSF
  4. SystemsX EpiPhysX grant
  5. ERC
  6. NCCR Chemical Biology program

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Research has found that scaling of the Dpp gradient in the Drosophila wing disc is achieved by increasing the contribution of internalized Dpp molecules to Dpp transport, regulated by the extracellular factor Pentagone. This evolutionary mechanism may act on endocytic trafficking to regulate the range and scaling of the gradient, allowing adaptation of shape and pattern to different sizes of organs in different species.
Morphogen gradients are fundamental to establish morphological patterns in developing tissues(1). During development, gradients scale to remain proportional to the size of growing organs(2,3). Scaling is a universal gear that adjusts patterns to size in living organisms(3-8), 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.

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