ZFIN ID: ZDB-PUB-140317-12
Toddler: an embryonic signal that promotes cell movement via Apelin receptors
Pauli, A., Norris, M.L., Valen, E., Chew, G.L., Gagnon, J.A., Zimmerman, S., Mitchell, A., Ma, J., Dubrulle, J., Reyon, D., Tsai, S.Q., Joung, J.K., Saghatelian, A., and Schier, A.F.
Date: 2014
Source: Science (New York, N.Y.)   343(6172): 1248636 (Journal)
Registered Authors: Dubrulle, Julien, Pauli, Andrea, Schier, Alexander, Zimmerman, Steve
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Cell Movement*
  • Chemokine CXCL12/metabolism
  • Frameshift Mutation
  • Gastrulation/genetics
  • Gastrulation/physiology*
  • Molecular Sequence Data
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism*
  • Signal Transduction
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 24407481 Full text @ Science

It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein–coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.