Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Koh, Woo Seuk, Knudsen, Collin, Izumikawa, Tomomi, Nakato, Eriko, Grandt, Kristin, Kinoshita-Toyoda, Akiko, Toyoda, Hidenao, Nakato, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2023
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
_version_ 1785027918776238080
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
work_keys_str_mv AT kohwooseuk regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT knudsencollin regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT izumikawatomomi regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT nakatoeriko regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT grandtkristin regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT kinoshitatoyodaakiko regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT toyodahidenao regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe
AT nakatohiroshi regulationofmorphogenpathwaysbyadrosophilachondroitinsulfateproteoglycanwindpipe