Failure in closure of the anterior neural tube causes left isomerization of the zebrafish epithalamus

Lu, P.N., Lund, C., Khuansuwan, S., Schumann, A., Harney-Tolo, M., Gamse, J.T., and Liang, J.O.
Developmental Biology   374(2): 333-344 (Journal)
Registered Authors
Gamse, Josh, Khuansuwan, Sataree, Liang, Jennifer
left-right asymmetry, zebrafish, epithalamus, neural tube defects, pineal gland, habenula nuclei
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cadherins/genetics
  • Cadherins/metabolism
  • Cell Differentiation/genetics
  • Cell Differentiation/physiology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Epithalamus/embryology
  • Epithalamus/metabolism
  • Epithalamus/physiology*
  • Functional Laterality/genetics
  • Functional Laterality/physiology
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Habenula/embryology
  • Habenula/metabolism
  • Humans
  • In Situ Hybridization
  • Mutation
  • Neural Tube/embryology
  • Neural Tube/metabolism
  • Neural Tube/physiology*
  • Nodal Protein/genetics
  • Nodal Protein/metabolism
  • Nodal Protein/physiology*
  • Pineal Gland/embryology
  • Pineal Gland/metabolism
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
23201575 Full text @ Dev. Biol.

Differences between the left and right sides of the brain are present in many animal species. For instance, in humans the left cerebral hemisphere is largely responsible for language and tool use and the right for processing spatial information. Zebrafish have prominent left–right asymmetries in their epithalamus that have been associated with differential left and right eye use and navigational behavior. In wild-type (WT) zebrafish embryos, Nodal pathway genes are expressed in the left side of the pineal anlage. Shortly thereafter, a parapineal organ forms to the left of the pineal. The parapineal organ causes differences in gene expression, neuropil density, and connectivity of the left and right habenula nuclei. In embryos that have an open neural tube, such as embryos that are deficient in Nodal signaling or the cell adhesion protein N-cadherin, the left and right sides of the developing epithalamus remain separated from one another. We find that the brains of these embryos become left isomerized: both sides of the brain develop morphology and gene expression patterns that are characteristic of the left side. However, other aspects of epithalamic development, such as differentiation of specific neuronal cell types, are intact. We propose that there is a mechanism in embryos with closed neural tubes that prevents both sides from developing like the left side. This mechanism fails when the two sides of the epithalamus are widely separated from one another, suggesting that it is dependent upon a signaling protein with limited range.

Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes