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Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe
Morphogens provide quantitative and robust signaling systems to achieve stereotypic patterning and morphogenesis. Heparan sulfate (HS) proteoglycans (HSPGs) are key components of such regulatory feedback networks. In Drosophila, HSPGs serve as co-receptors for a number of morphogens, including Hedge...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113886/ https://www.ncbi.nlm.nih.gov/pubmed/36897575 http://dx.doi.org/10.1242/jcs.260525 |
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author | Koh, Woo Seuk Knudsen, Collin Izumikawa, Tomomi Nakato, Eriko Grandt, Kristin Kinoshita-Toyoda, Akiko Toyoda, Hidenao Nakato, Hiroshi |
author_facet | Koh, Woo Seuk Knudsen, Collin Izumikawa, Tomomi Nakato, Eriko Grandt, Kristin Kinoshita-Toyoda, Akiko Toyoda, Hidenao Nakato, Hiroshi |
author_sort | Koh, Woo Seuk |
collection | PubMed |
description | Morphogens provide quantitative and robust signaling systems to achieve stereotypic patterning and morphogenesis. Heparan sulfate (HS) proteoglycans (HSPGs) are key components of such regulatory feedback networks. In Drosophila, HSPGs serve as co-receptors for a number of morphogens, including Hedgehog (Hh), Wingless (Wg), Decapentaplegic (Dpp) and Unpaired (Upd, or Upd1). Recently, Windpipe (Wdp), a chondroitin sulfate (CS) proteoglycan (CSPG), was found to negatively regulate Upd and Hh signaling. However, the roles of Wdp, and CSPGs in general, in morphogen signaling networks are poorly understood. We found that Wdp is a major CSPG with 4-O-sulfated CS in Drosophila. Overexpression of wdp modulates Dpp and Wg signaling, showing that it is a general regulator of HS-dependent pathways. Although wdp mutant phenotypes are mild in the presence of morphogen signaling buffering systems, this mutant in the absence of Sulf1 or Dally, molecular hubs of the feedback networks, produces high levels of synthetic lethality and various severe morphological phenotypes. Our study indicates a close functional relationship between HS and CS, and identifies the CSPG Wdp as a novel component in morphogen feedback pathways. |
format | Online Article Text |
id | pubmed-10113886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-101138862023-04-20 Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe Koh, Woo Seuk Knudsen, Collin Izumikawa, Tomomi Nakato, Eriko Grandt, Kristin Kinoshita-Toyoda, Akiko Toyoda, Hidenao Nakato, Hiroshi J Cell Sci Research Article Morphogens provide quantitative and robust signaling systems to achieve stereotypic patterning and morphogenesis. Heparan sulfate (HS) proteoglycans (HSPGs) are key components of such regulatory feedback networks. In Drosophila, HSPGs serve as co-receptors for a number of morphogens, including Hedgehog (Hh), Wingless (Wg), Decapentaplegic (Dpp) and Unpaired (Upd, or Upd1). Recently, Windpipe (Wdp), a chondroitin sulfate (CS) proteoglycan (CSPG), was found to negatively regulate Upd and Hh signaling. However, the roles of Wdp, and CSPGs in general, in morphogen signaling networks are poorly understood. We found that Wdp is a major CSPG with 4-O-sulfated CS in Drosophila. Overexpression of wdp modulates Dpp and Wg signaling, showing that it is a general regulator of HS-dependent pathways. Although wdp mutant phenotypes are mild in the presence of morphogen signaling buffering systems, this mutant in the absence of Sulf1 or Dally, molecular hubs of the feedback networks, produces high levels of synthetic lethality and various severe morphological phenotypes. Our study indicates a close functional relationship between HS and CS, and identifies the CSPG Wdp as a novel component in morphogen feedback pathways. The Company of Biologists Ltd 2023-04-11 /pmc/articles/PMC10113886/ /pubmed/36897575 http://dx.doi.org/10.1242/jcs.260525 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Koh, Woo Seuk Knudsen, Collin Izumikawa, Tomomi Nakato, Eriko Grandt, Kristin Kinoshita-Toyoda, Akiko Toyoda, Hidenao Nakato, Hiroshi Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe |
title | Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe |
title_full | Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe |
title_fullStr | Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe |
title_full_unstemmed | Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe |
title_short | Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe |
title_sort | regulation of morphogen pathways by a drosophila chondroitin sulfate proteoglycan windpipe |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113886/ https://www.ncbi.nlm.nih.gov/pubmed/36897575 http://dx.doi.org/10.1242/jcs.260525 |
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