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...
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doaj-40f4ecdd00cb451c9d1eb9d2ef66a5402021-05-05T13:55:37ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.22626Toddler signaling regulates mesodermal cell migration downstream of Nodal signalingMegan L Norris0https://orcid.org/0000-0003-0666-2665Andrea Pauli1https://orcid.org/0000-0001-9646-2303James A Gagnon2Nathan D Lord3Katherine W Rogers4Christian Mosimann5https://orcid.org/0000-0002-0749-2576Leonard I Zon6https://orcid.org/0000-0003-0860-926XAlexander F Schier7https://orcid.org/0000-0001-7645-5325Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, AustriaDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesInstitute of Molecular Life Sciences, University of Zürich, Zürich, SwitzerlandDivision of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, United States; Harvard Medical School, Boston, United States; Stem Cell Program, Boston Children's Hospital, Boston, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United States; Center for Brain Science, Harvard University, Cambridge, United States; The Broad Institute of Harvard and MIT, Cambridge, United States; FAS Center for Systems Biology, Harvard University, Cambridge, United StatesToddler/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.https://elifesciences.org/articles/22626ToddlerApelaElabelaCxcr4aNodalGastrulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Megan L Norris Andrea Pauli James A Gagnon Nathan D Lord Katherine W Rogers Christian Mosimann Leonard I Zon Alexander F Schier |
spellingShingle |
Megan L Norris Andrea Pauli James A Gagnon Nathan D Lord Katherine W Rogers Christian Mosimann Leonard I Zon Alexander F Schier Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling eLife Toddler Apela Elabela Cxcr4a Nodal Gastrulation |
author_facet |
Megan L Norris Andrea Pauli James A Gagnon Nathan D Lord Katherine W Rogers Christian Mosimann Leonard I Zon Alexander F Schier |
author_sort |
Megan L Norris |
title |
Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling |
title_short |
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_sort |
toddler signaling regulates mesodermal cell migration downstream of nodal signaling |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-11-01 |
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. |
topic |
Toddler Apela Elabela Cxcr4a Nodal Gastrulation |
url |
https://elifesciences.org/articles/22626 |
work_keys_str_mv |
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1721460475629142016 |