A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain

Neuron. 2000 Nov;28(2):399-409. doi: 10.1016/s0896-6273(00)00120-3.


Animals show behavioral asymmetries that are mediated by differences between the left and right sides of the brain. We report that the laterality of asymmetric development of the diencephalic habenular nuclei and the photoreceptive pineal complex is regulated by the Nodal signaling pathway and by midline tissue. Analysis of zebrafish embryos with compromised Nodal signaling reveals an early role for this pathway in the repression of asymmetrically expressed genes in the diencephalon. Later signaling mediated by the EGF-CFC protein One-eyed pinhead and the forkhead transcription factor Schmalspur is required to overcome this repression. When expression of Nodal pathway genes is either absent or symmetrical, neuroanatomical asymmetries are still established but are randomized. This indicates that Nodal signaling is not required for asymmetric development per se but is essential to determine the laterality of the asymmetry.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Diencephalon / anatomy & histology
  • Diencephalon / embryology
  • Fetal Proteins
  • Functional Laterality / genetics*
  • Gene Expression Regulation, Developmental
  • Habenula / anatomy & histology
  • Habenula / embryology
  • Habenula / metabolism
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Mutagenesis, Site-Directed
  • Nodal Protein
  • Nuclear Proteins*
  • Paired Box Transcription Factors
  • Pineal Gland / anatomy & histology
  • Pineal Gland / embryology
  • Pineal Gland / metabolism
  • Prosencephalon / anatomy & histology*
  • Prosencephalon / embryology*
  • Signal Transduction / genetics*
  • T-Box Domain Proteins / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Zebrafish
  • Zebrafish Proteins*


  • Fetal Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nodal Protein
  • Nuclear Proteins
  • Paired Box Transcription Factors
  • T-Box Domain Proteins
  • Transcription Factors
  • Transforming Growth Factor beta
  • Zebrafish Proteins
  • homeobox protein PITX1
  • homeobox protein PITX3
  • ndr2 protein, zebrafish
  • tdgf1 protein, zebrafish
  • homeobox protein PITX2
  • Brachyury protein