PUBLICATION

Six3 represses nodal activity to establish early brain asymmetry in zebrafish

Authors
Inbal, A., Kim, S.H., Shin, J., and Solnica-Krezel, L.
ID
ZDB-PUB-070813-10
Date
2007
Source
Neuron   55(3): 407-415 (Journal)
Registered Authors
Inbal, Adi, Kim, Seok-Hyung, Shin, Jimann, Solnica-Krezel, Lilianna
Keywords
none
MeSH Terms
  • Animals
  • Brain/embryology*
  • Dominance, Cerebral/physiology*
  • Embryonic Development/physiology*
  • Epistasis, Genetic
  • Epithalamus/embryology
  • Eye Proteins/physiology*
  • Homeodomain Proteins/physiology*
  • Nerve Tissue Proteins/physiology*
  • Nodal Protein
  • Transforming Growth Factor beta/antagonists & inhibitors
  • Zebrafish/embryology*
  • Zebrafish/genetics
PubMed
17678854 Full text @ Neuron
Abstract
The vertebrate brain is anatomically and functionally asymmetric; however, the molecular mechanisms that establish left-right brain patterning are largely unknown. In zebrafish, asymmetric left-sided Nodal signaling within the developing dorsal diencephalon is required for determining the direction of epithalamic asymmetries. Here, we show that Six3, a transcription factor essential for forebrain formation and associated with holoprosencephaly in humans, regulates diencephalic Nodal activity during initial establishment of brain asymmetry. Reduction of Six3 function causes brain-specific deregulation of Nodal pathway activity, resulting in epithalamic laterality defects. Based on misexpression and genetic epistasis experiments, we propose that Six3 acts in the neuroectoderm to establish a prepattern of bilateral repression of Nodal activity. Subsequently, Nodal signaling from the left lateral plate mesoderm alleviates this repression ipsilaterally. Our data reveal a Six3-dependent mechanism for establishment of correct brain laterality and provide an entry point to understanding the genetic regulation of Nodal signaling in the brain.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes