Formation of the long range Dpp morphogen gradient.
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Version: author
State: Public
Version: author
Serval ID
serval:BIB_745551B985EE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Formation of the long range Dpp morphogen gradient.
Journal
Plos Biology
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
9
Number
7
Pages
e1001111
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov' tPublication Status: ppublish
Abstract
The TGF-β homolog Decapentaplegic (Dpp) acts as a secreted morphogen in the Drosophila wing disc, and spreads through the target tissue in order to form a long range concentration gradient. Despite extensive studies, the mechanism by which the Dpp gradient is formed remains controversial. Two opposing mechanisms have been proposed: receptor-mediated transcytosis (RMT) and restricted extracellular diffusion (RED). In these scenarios the receptor for Dpp plays different roles. In the RMT model it is essential for endocytosis, re-secretion, and thus transport of Dpp, whereas in the RED model it merely modulates Dpp distribution by binding it at the cell surface for internalization and subsequent degradation. Here we analyzed the effect of receptor mutant clones on the Dpp profile in quantitative mathematical models representing transport by either RMT or RED. We then, using novel genetic tools, experimentally monitored the actual Dpp gradient in wing discs containing receptor gain-of-function and loss-of-function clones. Gain-of-function clones reveal that Dpp binds in vivo strongly to the type I receptor Thick veins, but not to the type II receptor Punt. Importantly, results with the loss-of-function clones then refute the RMT model for Dpp gradient formation, while supporting the RED model in which the majority of Dpp is not bound to Thick veins. Together our results show that receptor-mediated transcytosis cannot account for Dpp gradient formation, and support restricted extracellular diffusion as the main mechanism for Dpp dispersal. The properties of this mechanism, in which only a minority of Dpp is receptor-bound, may facilitate long-range distribution.
Keywords
Activin Receptors, Type II/genetics, Activin Receptors, Type II/metabolism, Algorithms, Animals, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/anatomy & histology, Drosophila melanogaster/genetics, Larva/genetics, Larva/growth & development, Models, Chemical, Morphogenesis, Mutation, Organ Specificity, Protein-Serine-Threonine Kinases/genetics, Protein-Serine-Threonine Kinases/metabolism, Receptors, Cell Surface/genetics, Receptors, Cell Surface/metabolism, Wing/growth & development, Wing/metabolism
Pubmed
Open Access
Yes
Create date
10/10/2014 14:55
Last modification date
20/08/2019 15:32