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Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling
Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The ‘specification model’ postulates that Toddler signaling enhances Nodal signaling to properly specif...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679751/ https://www.ncbi.nlm.nih.gov/pubmed/29117894 http://dx.doi.org/10.7554/eLife.22626 |
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author | Norris, Megan L Pauli, Andrea Gagnon, James A Lord, Nathan D Rogers, Katherine W Mosimann, Christian Zon, Leonard I Schier, Alexander F |
author_facet | Norris, Megan L Pauli, Andrea Gagnon, James A Lord, Nathan D Rogers, Katherine W Mosimann, Christian Zon, Leonard I Schier, Alexander F |
author_sort | Norris, Megan L |
collection | PubMed |
description | Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The ‘specification model’ postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the ‘migration model’ posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration. Mesodermal cell migration defects in toddler mutants result from a decrease in animal pole-directed migration and are independent of endoderm. Conversely, endodermal cell migration defects are dependent on a Cxcr4a-regulated tether of the endoderm to mesoderm. These results suggest that Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling and indirectly affects endodermal cell migration via Cxcr4a-signaling. |
format | Online Article Text |
id | pubmed-5679751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-56797512017-11-13 Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling Norris, Megan L Pauli, Andrea Gagnon, James A Lord, Nathan D Rogers, Katherine W Mosimann, Christian Zon, Leonard I Schier, Alexander F eLife Developmental Biology Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The ‘specification model’ postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the ‘migration model’ posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration. Mesodermal cell migration defects in toddler mutants result from a decrease in animal pole-directed migration and are independent of endoderm. Conversely, endodermal cell migration defects are dependent on a Cxcr4a-regulated tether of the endoderm to mesoderm. These results suggest that Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling and indirectly affects endodermal cell migration via Cxcr4a-signaling. eLife Sciences Publications, Ltd 2017-11-09 /pmc/articles/PMC5679751/ /pubmed/29117894 http://dx.doi.org/10.7554/eLife.22626 Text en © 2017, Norris et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Norris, Megan L Pauli, Andrea Gagnon, James A Lord, Nathan D Rogers, Katherine W Mosimann, Christian Zon, Leonard I Schier, Alexander F Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title | Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title_full | Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title_fullStr | Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title_full_unstemmed | Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title_short | Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title_sort | toddler signaling regulates mesodermal cell migration downstream of nodal signaling |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679751/ https://www.ncbi.nlm.nih.gov/pubmed/29117894 http://dx.doi.org/10.7554/eLife.22626 |
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