PUBLICATION

Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish

Authors: Reuter, I., Jäckels, J., Kneitz, S., Kuper, J., Lesch, K.P., Lillesaar, C.
ID: ZDB-PUB-190501-4
Date: 2019
Source: Biology Open 8(6): (Journal)
Registered Authors: Lillesaar, Christina
Keywords: Central nervous system, Dopamine, Fgf-signalling, Hypothalamus, Serotonin
MeSH Terms: none
PubMed: 31036752 Full text @ Biol. Open

Abstract

In most vertebrates, including zebrafish, the hypothalamic serotonergic cerebrospinal fluid-contacting (CSF-c) cells constitute a prominent population. In contrast to the hindbrain serotonergic neurons, little is known about the development and function of these cells. Here, we identify Fibroblast growth factor (Fgf)3 as the main Fgf ligand controlling the ontogeny of serotonergic CSF-c cells. We show that fgf3 positively regulates the number of serotonergic CSF-c cells, as well as a subset of dopaminergic and neuroendocrine cells in the posterior hypothalamus via control of proliferation and cell survival. Further, expression of the ETS-domain transcription factor etv5b is downregulated after fgf3 impairment. Previous findings identified etv5b as critical for the proliferation of serotonergic progenitors in the hypothalamus, and therefore we now suggest that Fgf3 acts via etv5b during early development to ultimately control the number of mature serotonergic CSF-c cells. Moreover, our analysis of the developing hypothalamic transcriptome shows that the expression of fgf3 is upregulated upon fgf3 loss-of-function, suggesting activation of a self-compensatory mechanism. Together, these results highlight Fgf3 in a novel context as part of a signalling pathway of critical importance for hypothalamic development.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
avp	AB	control	Protruding-mouth	hypothalamus neuron	ISH	Fig. 4.
avp	AB + MO9-fgf3	control	Protruding-mouth	hypothalamus neuron	ISH	Fig. 4.
avp	AB + MO9-fgf3	control	Protruding-mouth	hypothalamus	ISH	Fig. 4.
avp	fgf3^{t24152/t24152} (TU)	control	Protruding-mouth	hypothalamus neuron	ISH	Fig. 4.
avp	fgf3^{t24152/t24152} (TU)	control	Protruding-mouth	hypothalamus	ISH	Fig. 4.
avp	TU	control	Protruding-mouth	hypothalamus neuron	ISH	Fig. 4.
dusp6	AB	control	Pec-fin	hypothalamus	ISH	Fig. 1.
dusp6	AB	control	Prim-25	hypothalamus	ISH	Fig. 1.
dusp6	AB	control	Pec-fin	posterior recess anatomical region	ISH	Fig. 1.
dusp6	AB	control	Prim-25	posterior recess anatomical region	ISH	Fig. 1.

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + CRISPR2-fgf3 + CRISPR3-fgf3	control	Protruding-mouth	hypothalamus ab1-serotonin labeling decreased distribution, abnormal	Fig. 3.
AB + CRISPR2-fgf3 + CRISPR3-fgf3	control	Protruding-mouth	hypothalamus ab3-th labeling decreased distribution, abnormal	Fig. 3.
AB + CRISPR2-fgf3 + CRISPR3-fgf3	control	Protruding-mouth	hypothalamus dopaminergic neuron decreased amount, abnormal	Fig. 3.
AB + CRISPR2-fgf3 + CRISPR3-fgf3	control	Protruding-mouth	hypothalamus serotonergic neuron decreased amount, abnormal	Fig. 3.
AB + CRISPR2-fgf3 + CRISPR3-fgf3	control	Protruding-mouth	otolith fused with otolith, abnormal	Fig. S3
AB + CRISPR2-fgf3 + CRISPR3-fgf3	control	Protruding-mouth	ventral mandibular arch malformed, abnormal	Fig. S3
AB + MO9-fgf3	control	Prim-25	hypothalamus etv5b expression decreased amount, abnormal	Fig. 2.
AB + MO9-fgf3	control	Prim-25	hypothalamus nkx2.4b expression decreased distribution, abnormal	Fig. 5.
AB + MO9-fgf3	control	Prim-25	hypothalamus ab11-casp3 labeling increased distribution, abnormal	Fig. 6.
AB + MO9-fgf3	control	Prim-25	hypothalamus cell death increased occurrence, abnormal	Fig. 6.

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
t24152		Point Mutation	fgf3

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fgf3	CRISPR2-fgf3	CRISPR
fgf3	CRISPR3-fgf3	CRISPR
fgf3	MO9-fgf3	MRPHLNO

Fish

Fish
AB
AB + CRISPR2-fgf3 + CRISPR3-fgf3
AB + MO9-fgf3
fgf3^{t24152/t24152} (TU)
TU

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-serotonin	polyclonal			Rabbit
Ab3-th	monoclonal	th	IgG1	Mouse
Ab11-casp3	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Mapping

Reuter et al., 2019 ZDB-PUB-190501-4 PMID:31036752

Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish

Reuter et al., 2019

ZDB-PUB-190501-4
PMID:31036752