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Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling
Journal article

Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

  • Norris, Megan L ORCID Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
  • Pauli, Andrea ORCID Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria
  • Gagnon, James A Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
  • Lord, Nathan D Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
  • Rogers, Katherine W Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
  • Mosimann, Christian ORCID Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland
  • Zon, Leonard I ORCID Stem Cell Program, Boston Children's Hospital, Boston, United States
  • Schier, Alexander F ORCID FAS Center for Systems Biology, Harvard University, Cambridge, United States
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  • 2017-11-9
Published in:
  • eLife. - eLife Sciences Publications, Ltd. - 2017, vol. 6
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/253917
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