EphrinA5 Signaling Is Required for the Distinctive Targeting of Raphe Serotonin Neurons in the Forebrain

Autor: Patricia Gaspar, Teng Teng, Aude Muzerelle, Afsaneh Gaillard
Přispěvatelé: Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), BALLION, Bérangère
Jazyk: angličtina
Rok vydání: 2017
Předmět:
MESH: Signal Transduction
MESH: Ephrins
[SDV]Life Sciences [q-bio]
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Tryptophan Hydroxylase
MESH: Animals
Newborn
Mice
MESH: Prosencephalon
0302 clinical medicine
MESH: Amygdala
Neural Pathways
MESH: Gene Expression Regulation
Developmental
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
MESH: Animals
hypothalamus
MESH: Serotonin Plasma Membrane Transport Proteins
Cells
Cultured
Serotonin Plasma Membrane Transport Proteins
0303 health sciences
TPH2
General Neuroscience
Midbrain Raphe Nuclei
Serotonergic cell groups
Age Factors
Gene Expression Regulation
Developmental
General Medicine
amygdala
MESH: Transcription Factors
New Research
Ephrin-A5
[SDV] Life Sciences [q-bio]
Ephrin
olfactory bulb
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Ephrins
Signal Transduction
MESH: Cells
Cultured
Serotonin
MESH: Mice
Transgenic
Green Fluorescent Proteins
Mice
Transgenic
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Development
MESH: Ephrin-A5
03 medical and health sciences
Dorsal raphe nucleus
Prosencephalon
MESH: Green Fluorescent Proteins
Animals
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
MESH: Midbrain Raphe Nuclei
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
MESH: Mice
030304 developmental biology
MESH: Age Factors
Raphe
MESH: Neural Pathways
MESH: Embryo
Mammalian
Embryo
Mammalian
in utero electroporation
MESH: Tryptophan Hydroxylase
Olfactory bulb
culture
Animals
Newborn
nervous system
Forebrain
Ephrin A5
MESH: Serotonin
Raphe nuclei
Neuroscience
030217 neurology & neurosurgery
Transcription Factors
Zdroj: eNeuro
eNeuro, Society for Neuroscience, 2017, 4 (1), pp.ENEURO.0327-16.2017. ⟨10.1523/ENEURO.0327-16.2017⟩
eNeuro, 2017, 4 (1), pp.ENEURO.0327-16.2017. ⟨10.1523/ENEURO.0327-16.2017⟩
ISSN: 2373-2822
DOI: 10.1523/ENEURO.0327-16.2017⟩
Popis: Visual Abstract
Serotonin (5-HT) neurotransmission in the brain relies on a widespread axon terminal network originating from the hindbrain raphe nuclei. These projections are topographically organized such that the dorsal (DR), and median raphe (MnR) nuclei have different brain targets. However, the guidance molecules involved in this selective targeting in development are unknown. Here, we show the implication of ephrinA5 signaling in this process. We find that the EphA5 gene is selectively expressed in a subset of 5-HT neurons during embryonic and postnatal development. Highest coexpression of EphA5 and the 5-HT marker Tph2 is found in the DR, with lower coexpression in the MnR, and hardly any colocalization of the caudal raphe in the medulla. Accordingly, ephrinA induced a dose-dependent collapse response of 5-HT growth cones cultured from rostral but not caudal raphe. Ectopic expression of ephrinA3, after in utero electroporation in the amygdala and piriform cortex, repelled 5-HT raphe fiber ingrowth. Conversely, misplaced DR 5-HT axons were found in ephrin A5 knockout mice in brain regions that are normally only targeted by MnR 5-HT axons. This causes an overall increase in the density of 5-HT innervation in the ventromedial hypothalamus, the suprachiasmatic nucleus, and the olfactory bulb. All these brain areas have high expression of ephrinAs at the time of 5-HT fiber ingrowth. Present results show for the first time the role of a guidance molecule for the region-specific targeting of raphe neurons. This has important implications to understand how functional parsing of central 5-HT neurons is established during development.
Databáze: OpenAIRE
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