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
Citation
Inbal, A., Kim, S.H., Shin, J., and Solnica-Krezel, L. (2007) Six3 represses nodal activity to establish early brain asymmetry in zebrafish. Neuron. 55(3):407-415.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping