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Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development
Extracellular signals play essential roles during embryonic patterning by providing positional information in a concentration-dependent manner, and many such signals, like Wnt, fibroblast growth factor (FGF), Hedgehog (Hh), and retinoic acid, act by being secreted into the extracellular space, there...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960586/ https://www.ncbi.nlm.nih.gov/pubmed/33367974 http://dx.doi.org/10.1007/s00441-020-03318-2 |
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author | Kesavan, Gokul Raible, Florian Gupta, Mansi Machate, Anja Yilmaz, Dilara Brand, Michael |
author_facet | Kesavan, Gokul Raible, Florian Gupta, Mansi Machate, Anja Yilmaz, Dilara Brand, Michael |
author_sort | Kesavan, Gokul |
collection | PubMed |
description | Extracellular signals play essential roles during embryonic patterning by providing positional information in a concentration-dependent manner, and many such signals, like Wnt, fibroblast growth factor (FGF), Hedgehog (Hh), and retinoic acid, act by being secreted into the extracellular space, thereby triggering receptor-mediated responses in other cells. Isthmin1 (ism1) is a secreted protein whose gene expression pattern coincides with that of early dorsal determinants, nodal ligand genes like sqt and cyc, and with fgf8 during various phases of zebrafish development. Ism1 functions in early embryonic patterning and development are poorly understood; however, it has recently been shown to interact with nodal pathway genes to control organ asymmetry in chicken. Here, we show that misexpression of ism1 deletion constructs disrupts embryonic patterning in zebrafish and exhibits genetic interactions with both Fgf and nodal signaling. Unlike Fgf and nodal pathway mutants, CRISPR/Cas9-engineered ism1 mutants did not show obvious developmental defects. Further, in vivo single molecule fluorescence correlation spectroscopy (FCCS) showed that Ism1 diffuses freely in the extra-cellular space, with a diffusion coefficient similar to that of Fgf8a; however, our measurements do not support direct molecular interactions between Ism1 and either nodal ligands or Fgf8a in the developing zebrafish embryo. Together, data from gain- and loss-of-function experiments suggest that zebrafish Ism1 plays a complex role in regulating extracellular signals during early embryonic development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00441-020-03318-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7960586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-79605862021-04-01 Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development Kesavan, Gokul Raible, Florian Gupta, Mansi Machate, Anja Yilmaz, Dilara Brand, Michael Cell Tissue Res Regular Article Extracellular signals play essential roles during embryonic patterning by providing positional information in a concentration-dependent manner, and many such signals, like Wnt, fibroblast growth factor (FGF), Hedgehog (Hh), and retinoic acid, act by being secreted into the extracellular space, thereby triggering receptor-mediated responses in other cells. Isthmin1 (ism1) is a secreted protein whose gene expression pattern coincides with that of early dorsal determinants, nodal ligand genes like sqt and cyc, and with fgf8 during various phases of zebrafish development. Ism1 functions in early embryonic patterning and development are poorly understood; however, it has recently been shown to interact with nodal pathway genes to control organ asymmetry in chicken. Here, we show that misexpression of ism1 deletion constructs disrupts embryonic patterning in zebrafish and exhibits genetic interactions with both Fgf and nodal signaling. Unlike Fgf and nodal pathway mutants, CRISPR/Cas9-engineered ism1 mutants did not show obvious developmental defects. Further, in vivo single molecule fluorescence correlation spectroscopy (FCCS) showed that Ism1 diffuses freely in the extra-cellular space, with a diffusion coefficient similar to that of Fgf8a; however, our measurements do not support direct molecular interactions between Ism1 and either nodal ligands or Fgf8a in the developing zebrafish embryo. Together, data from gain- and loss-of-function experiments suggest that zebrafish Ism1 plays a complex role in regulating extracellular signals during early embryonic development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00441-020-03318-2) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-12-28 2021 /pmc/articles/PMC7960586/ /pubmed/33367974 http://dx.doi.org/10.1007/s00441-020-03318-2 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Regular Article Kesavan, Gokul Raible, Florian Gupta, Mansi Machate, Anja Yilmaz, Dilara Brand, Michael Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
title | Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
title_full | Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
title_fullStr | Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
title_full_unstemmed | Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
title_short | Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
title_sort | isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960586/ https://www.ncbi.nlm.nih.gov/pubmed/33367974 http://dx.doi.org/10.1007/s00441-020-03318-2 |
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