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Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc

How morphogen gradients control patterning and growth in developing tissues remains largely unknown due to lack of tools manipulating morphogen gradients. Here, we generate two membrane-tethered protein binders that manipulate different aspects of Decapentaplegic (Dpp), a morphogen required for over...

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Autores principales: Matsuda, Shinya, Schaefer, Jonas V., Mii, Yusuke, Hori, Yutaro, Bieli, Dimitri, Taira, Masanori, Plückthun, Andreas, Affolter, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576045/
https://www.ncbi.nlm.nih.gov/pubmed/34750371
http://dx.doi.org/10.1038/s41467-021-26726-6
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author Matsuda, Shinya
Schaefer, Jonas V.
Mii, Yusuke
Hori, Yutaro
Bieli, Dimitri
Taira, Masanori
Plückthun, Andreas
Affolter, Markus
author_facet Matsuda, Shinya
Schaefer, Jonas V.
Mii, Yusuke
Hori, Yutaro
Bieli, Dimitri
Taira, Masanori
Plückthun, Andreas
Affolter, Markus
author_sort Matsuda, Shinya
collection PubMed
description How morphogen gradients control patterning and growth in developing tissues remains largely unknown due to lack of tools manipulating morphogen gradients. Here, we generate two membrane-tethered protein binders that manipulate different aspects of Decapentaplegic (Dpp), a morphogen required for overall patterning and growth of the Drosophila wing. One is “HA trap” based on a single-chain variable fragment (scFv) against the HA tag that traps HA-Dpp to mainly block its dispersal, the other is “Dpp trap” based on a Designed Ankyrin Repeat Protein (DARPin) against Dpp that traps Dpp to block both its dispersal and signaling. Using these tools, we found that, while posterior patterning and growth require Dpp dispersal, anterior patterning and growth largely proceed without Dpp dispersal. We show that dpp transcriptional refinement from an initially uniform to a localized expression and persistent signaling in transient dpp source cells render the anterior compartment robust against the absence of Dpp dispersal. Furthermore, despite a critical requirement of dpp for the overall wing growth, neither Dpp dispersal nor direct signaling is critical for lateral wing growth after wing pouch specification. These results challenge the long-standing dogma that Dpp dispersal is strictly required to control and coordinate overall wing patterning and growth.
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spelling pubmed-85760452021-11-19 Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc Matsuda, Shinya Schaefer, Jonas V. Mii, Yusuke Hori, Yutaro Bieli, Dimitri Taira, Masanori Plückthun, Andreas Affolter, Markus Nat Commun Article How morphogen gradients control patterning and growth in developing tissues remains largely unknown due to lack of tools manipulating morphogen gradients. Here, we generate two membrane-tethered protein binders that manipulate different aspects of Decapentaplegic (Dpp), a morphogen required for overall patterning and growth of the Drosophila wing. One is “HA trap” based on a single-chain variable fragment (scFv) against the HA tag that traps HA-Dpp to mainly block its dispersal, the other is “Dpp trap” based on a Designed Ankyrin Repeat Protein (DARPin) against Dpp that traps Dpp to block both its dispersal and signaling. Using these tools, we found that, while posterior patterning and growth require Dpp dispersal, anterior patterning and growth largely proceed without Dpp dispersal. We show that dpp transcriptional refinement from an initially uniform to a localized expression and persistent signaling in transient dpp source cells render the anterior compartment robust against the absence of Dpp dispersal. Furthermore, despite a critical requirement of dpp for the overall wing growth, neither Dpp dispersal nor direct signaling is critical for lateral wing growth after wing pouch specification. These results challenge the long-standing dogma that Dpp dispersal is strictly required to control and coordinate overall wing patterning and growth. Nature Publishing Group UK 2021-11-08 /pmc/articles/PMC8576045/ /pubmed/34750371 http://dx.doi.org/10.1038/s41467-021-26726-6 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Matsuda, Shinya
Schaefer, Jonas V.
Mii, Yusuke
Hori, Yutaro
Bieli, Dimitri
Taira, Masanori
Plückthun, Andreas
Affolter, Markus
Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
title Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
title_full Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
title_fullStr Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
title_full_unstemmed Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
title_short Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
title_sort asymmetric requirement of dpp/bmp morphogen dispersal in the drosophila wing disc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576045/
https://www.ncbi.nlm.nih.gov/pubmed/34750371
http://dx.doi.org/10.1038/s41467-021-26726-6
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