ZFIN ID: ZDB-PUB-160709-12
Habenular Neurogenesis in Zebrafish Is Regulated by a Hedgehog, Pax6 Proneural Gene Cascade
Halluin, C., Madelaine, R., Naye, F., Peers, B., Roussigné, M., Blader, P.
Date: 2016
Source: PLoS One   11: e0158210 (Journal)
Registered Authors: Blader, Patrick, Halluin, Caroline, Peers, Bernard, Roussigné, Myriam
Keywords: Embryos, Hedgehog signaling, Neurogenesis, Neurons, Zebrafish, Diencephalon, Developmental signaling, In situ hybridization
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors/physiology
  • Body Patterning
  • Gene Expression Regulation, Developmental
  • Genotype
  • Habenula/embryology*
  • Hedgehog Proteins/physiology*
  • Heterozygote
  • Mutation
  • Nerve Tissue Proteins/physiology
  • Neurogenesis*
  • Neurons/metabolism
  • PAX6 Transcription Factor/physiology*
  • Polymerase Chain Reaction
  • Signal Transduction*
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish Proteins/physiology*
PubMed: 27387288 Full text @ PLoS One
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ABSTRACT
The habenulae are highly conserved nuclei in the dorsal diencephalon that connect the forebrain to the midbrain and hindbrain. These nuclei have been implicated in a broad variety of behaviours in humans, primates, rodents and zebrafish. Despite this, the molecular mechanisms that control the genesis and differentiation of neural progenitors in the habenulae remain relatively unknown. We have previously shown that, in zebrafish, the timing of habenular neurogenesis is left-right asymmetric and that in the absence of Nodal signalling this asymmetry is lost. Here, we show that habenular neurogenesis requires the homeobox transcription factor Pax6a and the redundant action of two proneural bHLH factors, Neurog1 and Neurod4. We present evidence that Hedgehog signalling is required for the expression of pax6a, which is in turn necessary for the expression of neurog1 and neurod4. Finally, we demonstrate by pharmacological inhibition that Hedgehog signalling is required continuously during habenular neurogenesis and by cell transplantation experiments that pathway activation is required cell autonomously. Our data sheds light on the mechanism underlying habenular development that may provide insights into how Nodal signalling imposes asymmetry on the timing of habenular neurogenesis.
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