The Head Inducer Cerberus Is a Multifunctional Antagonist of Nodal, BMP and Wnt Signals

Nature. 1999 Feb 25;397(6721):707-10. doi: 10.1038/17820.

Abstract

Embryological and genetic evidence indicates that the vertebrate head is induced by a different set of signals from those that organize trunk-tail development. The gene cerberus encodes a secreted protein that is expressed in anterior endoderm and has the unique property of inducing ectopic heads in the absence of trunk structures. Here we show that the cerberus protein functions as a multivalent growth-factor antagonist in the extracellular space: it binds to Nodal, BMP and Wnt proteins via independent sites. The expression of cerberus during gastrulation is activated by earlier nodal-related signals in endoderm and by Spemann-organizer factors that repress signalling by BMP and Wnt. In order for the head territory to form, we propose that signals involved in trunk development, such as those involving BMP, Wnt and Nodal proteins, must be inhibited in rostral regions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / antagonists & inhibitors*
  • Bone Morphogenetic Proteins / genetics
  • Embryonic Induction*
  • Head / embryology
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Binding
  • Proteins / genetics
  • Proteins / physiology*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Wnt Proteins
  • Xenopus
  • Xenopus Proteins
  • Zebrafish Proteins*

Substances

  • Bone Morphogenetic Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • cer1 protein, Xenopus
  • ndr2 protein, zebrafish
  • nodal1 protein, Xenopus