Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target

Gamse, J.T., Kuan, Y.S., Macurak, M., Brosamle, C., Thisse, B., Thisse, C., and Halpern, M.E.
Development (Cambridge, England)   132(21): 4869-4881 (Journal)
Registered Authors
Gamse, Josh, Halpern, Marnie E., Kuan, Yung-Shu, Macurak, Michelle, Thisse, Bernard, Thisse, Christine
KCTD gene family, leftover gene, Left-right asymmetry, Habenular nuclei, Fasciculus retroflexus, Interpeduncular nucleus, Diencephalon
MeSH Terms
  • Animals
  • Body Patterning*
  • Embryo, Nonmammalian
  • Epithalamus/embryology*
  • Epithalamus/physiology
  • Habenula/embryology
  • Mesencephalon/embryology*
  • Nervous System/embryology*
  • Neurons
  • Pineal Gland/embryology
  • Zebrafish/embryology
16207761 Full text @ Development
The zebrafish epithalamus, consisting of the pineal complex and flanking dorsal habenular nuclei, provides a valuable model for exploring how left-right differences could arise in the vertebrate brain. The parapineal lies to the left of the pineal and the left habenula is larger, has expanded dense neuropil, and distinct patterns of gene expression from the right habenula. Under the influence of Nodal signaling, positioning of the parapineal sets the direction of habenular asymmetry and thereby determines the left-right origin of habenular projections onto the midbrain target, the interpeduncular nucleus (IPN). In zebrafish with parapineal reversal, neurons from the left habenula project to a more limited ventral IPN region where right habenular axons would normally project. Conversely, efferents from the right habenula adopt a more extensive dorsoventral IPN projection pattern typical of left habenular neurons. Three members of the leftover-related KCTD (potassium channel tetramerization domain containing) gene family are expressed differently by the left and right habenula, in patterns that define asymmetric subnuclei. Molecular asymmetry extends to protein levels in habenular efferents, providing additional evidence that left and right axons terminate within different dorsoventral regions of the midbrain target. Laser-mediated ablation of the parapineal disrupts habenular asymmetry and consequently alters the dorsoventral distribution of innervating axons. The results demonstrate that laterality of the dorsal forebrain influences the formation of midbrain connections and their molecular properties.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes