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Development. 2013 Jan 15;140(2):372-84. doi: 10.1242/dev.089094.

Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b.

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  • 1Zebrafish Neurogenetics Group, Laboratory of Neurobiology and Development, CNRS UPR3294, Institute of Neurobiology Albert Fessard, 1 Avenue de Terrasse, 91198 Gif-sur-Yvette, France.


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.

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