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

Po Nien Lu, Caroline Lund, Sataree Khuansuwan, Adelle Schumann, Marijah Harney-Tolo, Joshua T. Gamse, Jennifer O Liang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 often 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.

Original languageEnglish (US)
Pages (from-to)333-344
Number of pages12
JournalDevelopmental Biology
Issue number2
StatePublished - Feb 15 2013

Bibliographical note

Funding Information:
Our thanks to Dr. Radhika Atit and Dr. Ronald Conlon for their valuable comments in this manuscript. Drs. Marnie Halpern, Rachel Brewster, Thomas Schilling, Patrick Blader generously shared reagents. This work was supported in part by research grant 1 RO1 HD054523 (to JTG and JOL) and a University of Minnesota Grant in Aid of Research and Scholarship (to JOL).


  • Epithalamus
  • Habenula nuclei
  • Left-right asymmetry
  • Neural tube defects
  • Pineal gland
  • Zebrafish


Dive into the research topics of 'Failure in closure of the anterior neural tube causes left isomerization of the zebrafish epithalamus'. Together they form a unique fingerprint.

Cite this