Expansion-repression mechanism for scaling the Dpp activation gradient in drosophila wing imaginal discs

Danny Ben-Zvi, George Pyrowolakis, Naama Barkai*, Ben Zion Shilo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Maintaining a proportionate body plan requires the adjustment or scaling of organ pattern with organ size. Scaling is a general property of developmental systems, yet little is known about its underlying molecular mechanisms. Using theoretical modeling, we examine how the Dpp activation gradient in the Drosophila wing imaginal disc scales with disc size. We predict that scaling is achieved through an expansion-repression mechanism [1] whose mediator is the widely diffusible protein Pentagone (Pent). Central to this mechanism is the repression of pent expression by Dpp signaling, which provides an effective size measurement, and the Pent-dependent expansion of the Dpp gradient, which adjusts the gradient with tissue size. We validate this mechanism experimentally by demonstrating that scaling requires Pent and further, that scaling is abolished when pent is ubiquitously expressed. The expansion-repression circuit can be readily implemented by a variety of molecular interactions, suggesting its general utilization for scaling morphogen gradients during development.

Original languageAmerican English
Pages (from-to)1391-1396
Number of pages6
JournalCurrent Biology
Volume21
Issue number16
DOIs
StatePublished - 23 Aug 2011
Externally publishedYes

Bibliographical note

Funding Information:
We thank E. Laufer for the pSmad1/5/8 antibody and the members of our groups for discussions and help with the experiments and analysis. D.B.-Z. is supported by the Adams Fellowship Program of the Israeli Academy of Sciences and Humanities. This work was supported by the European Research Council, Israel Science Foundation, Minerva, and the Helen and Martin Kimmel Award for Innovative Investigations to N.B. B.-Z.S. holds the Hilda and Cecil Lewis Professorial Chair in Molecular Genetics.

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