Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kesavan, Gokul, Raible, Florian, Gupta, Mansi, Machate, Anja, Yilmaz, Dilara, Brand, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
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
_version_ 1783665082948911104
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
work_keys_str_mv AT kesavangokul isthmin1asecretedsignalingproteinactsdownstreamofdiverseembryonicpatterningcentersindevelopment
AT raibleflorian isthmin1asecretedsignalingproteinactsdownstreamofdiverseembryonicpatterningcentersindevelopment
AT guptamansi isthmin1asecretedsignalingproteinactsdownstreamofdiverseembryonicpatterningcentersindevelopment
AT machateanja isthmin1asecretedsignalingproteinactsdownstreamofdiverseembryonicpatterningcentersindevelopment
AT yilmazdilara isthmin1asecretedsignalingproteinactsdownstreamofdiverseembryonicpatterningcentersindevelopment
AT brandmichael isthmin1asecretedsignalingproteinactsdownstreamofdiverseembryonicpatterningcentersindevelopment