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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 ML Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
  • Pauli A Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
  • Gagnon JA Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
  • Lord ND Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
  • Rogers KW Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
  • Mosimann C Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
  • Zon LI Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, United States.
  • Schier AF Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
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  • 2017-11-10
Published in:
  • eLife. - 2017
Apela
Cxcr4a
Elabela
Gastrulation
Nodal
Toddler
developmental biology
stem cells
zebrafish
Animals
Cell Movement
Gene Knockout Techniques
Mesoderm
Nodal Signaling Ligands
Receptors, CXCR4
Signal Transduction
Zebrafish
Zebrafish Proteins
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/47399
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