Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b
- Authors
- Bosco, A., Bureau, C., Affaticati, P., Gaspar, P., Bally-Cuif, L., and Lillesaar, C.
- ID
- ZDB-PUB-121221-3
- 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.