PUBLICATION

Neurotrophin receptor Ntrk2b function in the maintenance of dopamine and serotonin neurons in zebrafish

Authors

Sahu, M.P., Pazos-Boubeta, Y., Pajanoja, C., Rozov, S., Panula, P., Castrén, E.

ID

ZDB-PUB-190216-5

Date

2019

Source

Scientific Reports 9: 2036 (Journal)

Registered Authors

Keywords

none

MeSH Terms

Dopamine/metabolism
Zebrafish/metabolism
Animals
Neurons/metabolism
Brain-Derived Neurotrophic Factor/metabolism
Protein Isoforms
Signal Transduction
Receptor, trkB/metabolism*
Zebrafish Proteins/metabolism*
Serotonin/metabolism
Transcription Factors/metabolism
Serotonergic Neurons/metabolism*
Larva/metabolism
Dopaminergic Neurons/metabolism*
Brain/metabolism
Embryo, Nonmammalian/metabolism

(all 16)

PubMed

30765816 Full text @ Sci. Rep.

Abstract

Neurotrophins and their receptors have highly conserved evolutionary lineage in vertebrates including zebrafish. The NTRK2 receptor has two isoforms in zebrafish, Ntrk2a and Ntrk2b. The spatio-temporal expression pattern of bdnf and ntrk2b in the zebrafish brain was studied using in situ hybridization. The robust and corresponding expression pattern of ntrk2b to bdnf suggests that ntrk2b is the key receptor for bdnf in the zebrafish brain, unlike its duplicate isoform ntrk2a. To study ntrk2b function, two different genetic strategies, the TILLING mutant and morpholino oligonucleotides (MO), were used. Specific subsets of the dopaminergic and serotonergic neuronal populations were affected in the mutants and morphants. The mutant showed anxiety- like behavior both in larval and adult stages. Our results consistently indicate that BDNF/NTRK2 signaling has a significant role in the development and maintenance of aminergic neuronal populations. Therefore, the ntrk2b-deficient zebrafish is well suited to study mechanisms relevant for psychiatric disorders attributed to a dysfunctional monoaminergic system.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bdnf	WT	standard conditions	Adult	caudal tuberculum	ISH	Fig. 1
bdnf	WT	standard conditions	Adult	cerebellum	ISH	Fig. 1
bdnf	WT	standard conditions	Adult	dorsal telencephalon	ISH	Fig. 1
bdnf	WT	standard conditions	Adult	hypothalamus	ISH	Fig. 1
bdnf	WT	standard conditions	Adult	medulla oblongata	ISH	Fig. 1
bdnf	WT	standard conditions	Protruding-mouth	otic vesicle	ISH	Fig. 1
bdnf	WT	standard conditions	Protruding-mouth	preoptic area	ISH	Fig. 1
bdnf	WT	standard conditions	Protruding-mouth	rhombomere	ISH	Fig. 1
bdnf	WT	standard conditions	Protruding-mouth	telencephalon	ISH	Fig. 1
bdnf	WT	standard conditions	Long-pec	whole organism	RTPCR	Fig. 2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-ntrk2a	standard conditions	Day 5	caudal periventricular hypothalamus has normal numbers of parts of type caudal periventricular hypothalamus serotonergic neuron, normal	Fig. 6
WT + MO1-ntrk2a	standard conditions	Day 5	diencephalon ventral region has normal numbers of parts of type diencephalon dopaminergic neuron, normal	Fig. 4
WT + MO1-ntrk2a	standard conditions	Day 5	paraventricular organ has normal numbers of parts of type paraventricular organ serotonergic neuron, normal	Fig. 6
WT + MO2-ntrk2b	control	Protruding-mouth	whole organism th2 expression decreased amount, abnormal	Fig. 3
WT + MO2-ntrk2b	standard conditions	Prim-5	whole organism morphology, normal	Fig. 2
WT + MO2-ntrk2b	standard conditions	Prim-5	whole organism size, normal	Fig. 2
WT + MO2-ntrk2b	standard conditions	Long-pec	whole organism bdnf expression decreased amount, abnormal	Fig. 2
WT + MO2-ntrk2b	standard conditions	Long-pec	whole organism ntrk2b expression decreased amount, abnormal	Fig. 2
WT + MO2-ntrk2b	standard conditions	Protruding-mouth	caudal tuberculum ventral region slc6a4a expression absent, abnormal	Fig. 5
WT + MO2-ntrk2b	standard conditions	Protruding-mouth	diencephalon dopaminergic neuron th2 expression decreased amount, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
sa13660		Point Mutation	ntrk2b

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
ntrk2a	MO1-ntrk2a	MRPHLNO
ntrk2b	MO2-ntrk2b	MRPHLNO
ntrk2b	MO3-ntrk2b	MRPHLNO

Fish

Fish
ntrk2b^{sa13660/sa13660}
WT
WT + MO1-ntrk2a
WT + MO2-ntrk2b

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-ntrk	polyclonal	ntrk2b		Rabbit
Ab1-serotonin	polyclonal			Rabbit
Ab1-th	monoclonal	th	IgG1	Mouse
Ab2-ntrk	monoclonal		IgG	Rabbit
Ab3-gapdh	polyclonal		IgG	Rabbit
Ab4-actb	monoclonal		IgG2a	Mouse
Ab4-ntrk2	monoclonal		IgG1	Mouse
Ab5-ntrk2	polyclonal		IgG	Goat

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Orthology

Engineered Foreign Genes

Mapping

Sahu et al., 2019 ZDB-PUB-190216-5 PMID:30765816

Neurotrophin receptor Ntrk2b function in the maintenance of dopamine and serotonin neurons in zebrafish

Sahu et al., 2019

ZDB-PUB-190216-5
PMID:30765816