title: Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b.
abstract: 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.
authors.affiliation: Zebrafish Neurogenetics Group, Laboratory of Neurobiology and Development, CNRS UPR3294, Institute of Neurobiology Albert Fessard, 1 Avenue de Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bosco
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bureau
authors.forename: Pierre
authors.initials: P
authors.lastname: Affaticati
authors.forename: Patricia
authors.initials: P
authors.lastname: Gaspar
authors.forename: Laure
authors.initials: L
authors.lastname: Bally-Cuif
authors.forename: Christina
authors.initials: C
authors.lastname: Lillesaar
mesh_terms: D000818:Animals; D001692:Biological Transport; D002453:Cell Cycle; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D011903:Raphe Nuclei / Q000378:metabolism; D059326:Serotonergic Neurons / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: C521369:FEV protein, zebrafish; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D029961:Zebrafish Proteins; D012701:Serotonin; D005346:Fibroblast Growth Factors