ZFIN ID: ZDB-PUB-121221-3
Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b
Bosco, A., Bureau, C., Affaticati, P., Gaspar, P., Bally-Cuif, L., and Lillesaar, C.
Date: 2013
Source: Development (Cambridge, England)   140(2): 372-384 (Journal)
Registered Authors: Bally-Cuif, Laure, Bosco, Adriana, Lillesaar, Christina
Keywords: Etv5b (Erm), serotonin (5-hydroxytryptamine), fgf signalling, zebrafish
MeSH Terms:
  • Animals
  • Biological Transport
  • Cell Cycle
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression Regulation, Developmental*
  • Models, Biological
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-ets/metabolism*
  • Raphe Nuclei/metabolism
  • Serotonergic Neurons/metabolism*
  • Serotonin/metabolism*
  • Signal Transduction
  • Stem Cells/cytology
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 23250211 Full text @ Development

Serotonin is a monoamine neurotransmitter that is involved in numerous physiological functions and its dysregulation is implicated in various psychiatric diseases. In all non-placental vertebrates, serotoninergic (5-HT) neurons are present in several regions of the brain, including the hypothalamus. In placental mammals, however, 5-HT neurons are located in the raphe nuclei only. In all species, though, 5-HT neurons constitute a functionally and molecularly heterogeneous population. How the non-raphe 5-HT populations are developmentally encoded is unknown. Using the zebrafish model we show that, in contrast to the raphe populations, hypothalamic 5-HT neurons are generated independently of the ETS-domain transcription factor Pet1 (Fev). By applying a combination of pharmacological tools and gene knockdown and/or overexpression experiments, we demonstrate that Fgf signalling acts via another ETS-domain transcription factor, Etv5b (Erm), to induce hypothalamic 5-HT neurons. We provide evidence that Etv5b exerts its effects by regulating cell cycle parameters in 5-HT progenitors. Our results highlight a novel role for Etv5b in neuronal development and provide support for the existence of a developmental heterogeneity among 5-HT neurons in their requirement for ETS-domain transcription factors.