The zebrafish Nodal signal Squint functions as a morphogen

Nature. 2001 May 31;411(6837):607-10. doi: 10.1038/35079121.


Secreted morphogens induce distinct cellular responses in a concentration-dependent manner and act directly at a distance. The existence of morphogens during mesoderm induction and patterning in vertebrates has been highly controversial, and it remains unknown whether endogenous mesoderm inducers act directly as morphogens, function locally or act through relay mechanisms. Here we test the morphogen properties of Cyclops and Squint-two Nodal-related transforming growth factor-beta signals required for mesoderm formation and patterning in zebrafish. Whereas different levels of both Squint and Cyclops can induce different downstream genes, we find that only Squint can function directly at a distance. These results indicate that Squint acts as a secreted morphogen that does not require a relay mechanism.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Cell Communication
  • Embryo, Nonmammalian
  • Fetal Proteins
  • Gene Expression Regulation, Developmental
  • Intracellular Signaling Peptides and Proteins
  • Mesoderm / physiology
  • Morphogenesis
  • Nodal Protein
  • Nodal Signaling Ligands
  • Recombinant Fusion Proteins
  • Signal Transduction*
  • T-Box Domain Proteins / genetics
  • Transforming Growth Factor beta / physiology*
  • Zebrafish
  • Zebrafish Proteins*


  • Fetal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nodal Protein
  • Nodal Signaling Ligands
  • Recombinant Fusion Proteins
  • T-Box Domain Proteins
  • Transforming Growth Factor beta
  • Zebrafish Proteins
  • ndr1 protein, zebrafish
  • ndr2 protein, zebrafish
  • Brachyury protein