title: Toddler: an embryonic signal that promotes cell movement via Apelin receptors.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pauli
authors.forename: Megan L
authors.initials: ML
authors.lastname: Norris
authors.forename: Eivind
authors.initials: E
authors.lastname: Valen
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Chew
authors.forename: James A
authors.initials: JA
authors.lastname: Gagnon
authors.forename: Steven
authors.initials: S
authors.lastname: Zimmerman
authors.forename: Andrew
authors.initials: A
authors.lastname: Mitchell
authors.forename: Jiao
authors.initials: J
authors.lastname: Ma
authors.forename: Julien
authors.initials: J
authors.lastname: Dubrulle
authors.forename: Deepak
authors.initials: D
authors.lastname: Reyon
authors.forename: Shengdar Q
authors.initials: SQ
authors.lastname: Tsai
authors.forename: J Keith
authors.initials: JK
authors.lastname: Joung
authors.forename: Alan
authors.initials: A
authors.lastname: Saghatelian
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000075244:Apelin Receptors; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D016368:Frameshift Mutation; D054262:Gastrulation / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000075244:Apelin Receptors; D054377:Chemokine CXCL12; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C519093:apelin receptor, zebrafish; C579453:cxcl12a protein, zebrafish; C586716:toddler peptide, zebrafish