PUBLICATION

Zebrafish Wtx is a negative regulator of Wnt signaling but is dispensable for embryonic development and organ homeostasis

Authors

Große, A., Perner, B., Naumann, U., Englert, C.

ID

ZDB-PUB-190712-5

Date

2019

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 248(9): 866-881 (Journal)

Registered Authors

Englert, Christoph, Perner, Birgit

Keywords

Amer, Antisense Morpholino, TALENs, Wilms tumor gene

MeSH Terms

Homeostasis*
Regeneration
Mutant Proteins/pharmacology
Zebrafish
Embryonic Development*
Wnt Signaling Pathway/drug effects*
Embryo, Nonmammalian
Animals
Adaptor Proteins, Signal Transducing/genetics
Adaptor Proteins, Signal Transducing/physiology*

(all 10)

PubMed

31290212 Full text @ Dev. Dyn.

Abstract

Background The X-chromosomally linked gene WTX is a human disease gene and a member of the AMER family. Mutations in WTX are found in Wilms tumor, a form of pediatric kidney cancer and in patients suffering from OSCS (Osteopathia striata with cranial sclerosis), a sclerosing bone disorder. Functional data suggest WTX to be an inhibitor of the Wnt/β-catenin signaling pathway. Deletion of Wtx in mouse leads to perinatal death, impeding the analysis of its physiological role.

Results To gain insights into the function of Wtx in development and homeostasis we have used zebrafish as a model and performed both knockdown and knockout studies using morpholinos and transcription activator-like effector nucleases (TALENs), respectively. Wtx knockdown led to increased Wnt activity and embryonic dorsalization. Also, wtx mutants showed a transient upregulation of Wnt target genes in the context of caudal fin regeneration. Surprisingly, however, wtx as well as wtx/amer2/amer3 triple mutants developed normally, were fertile and did not show any anomalies in organ maintenance.

Conclusions Our data show that members of the zebrafish wtx/amer gene family, while sharing a partially overlapping expression pattern do not compensate for each other. This observation demonstrates a remarkable robustness during development and regeneration in zebrafish. This article is protected by copyright. All rights reserved.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
amer1	amer2^li19/li19	amputation: caudal fin	Adult	regenerating fin	RTPCR	Fig. 5
amer1	WT	standard conditions	Adult	adipose tissue	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	brain	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	caudal fin	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	gut	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	integument	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	kidney	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	liver	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	muscle	RTPCR	Fig. 1
amer1	WT	standard conditions	Adult	ovary	RTPCR	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-amer1	standard conditions	5-9 somites	anterior neural rod six3b expression increased distribution, abnormal	Fig. 2
WT + MO2-amer1	standard conditions	5-9 somites	anterior neural rod six3b expression spatial pattern, abnormal	Fig. 2
WT + MO2-amer1	standard conditions	5-9 somites	midbrain hindbrain boundary neural plate pax2a expression decreased distribution, abnormal	Fig. 2
WT + MO2-amer1	standard conditions	5-9 somites	midbrain hindbrain boundary neural plate pax2a expression spatial pattern, abnormal	Fig. 2
WT + MO2-amer1	standard conditions	5-9 somites	somite myod1 expression absent, abnormal	Fig. 2
WT + MO2-ctnnb2	standard conditions	5-9 somites	anterior neural rod six3b expression decreased amount, abnormal	Fig. 2
WT + MO2-ctnnb2	standard conditions	5-9 somites	anterior neural rod six3b expression spatial pattern, abnormal	Fig. 2
WT + MO2-ctnnb2	standard conditions	5-9 somites	midbrain hindbrain boundary neural plate pax2a expression decreased distribution, abnormal	Fig. 2
WT + MO2-ctnnb2	standard conditions	5-9 somites	midbrain hindbrain boundary neural plate pax2a expression spatial pattern, abnormal	Fig. 2
WT + MO2-ctnnb2	standard conditions	5-9 somites	segmental plate myod1 expression absent, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ia5Tg	Tg(7xTCF-Xla.Sia:NLS-mCherry)	Transgenic Insertion
li1Tg	Tg(wt1b:EGFP)	Transgenic Insertion
li15		Small Deletion	amer1
li16		Small Deletion	amer1
li17		Small Deletion	amer1
li18		Small Deletion	amer2
li19		Small Deletion	amer2
li20		Indel	amer3
w25Tg	Tg(top:GFP)	Transgenic Insertion

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
amer1	MO2-amer1	MRPHLNO
amer1	MO3-amer1	MRPHLNO
amer1	TALEN1-amer1	TALEN
amer1	TALEN2-amer1	TALEN
amer2	TALEN1-amer2	TALEN
amer3	TALEN1-amer3	TALEN
ctnnb2	MO2-ctnnb2	MRPHLNO
tp53	MO4-tp53	MRPHLNO

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Fish

Fish
amer1^li15/li15; ia5Tg
amer1^li17/li17
amer1^li17/li17; amer2^li18/li18; amer3^li20/li20
amer1^li17/li17; amer2^li18/li18; amer3^li20/li20 + MO3-amer1
amer1^li17/li17; li1Tg
amer2^li19/li19
amer3^li20/li20
ia5Tg
w25Tg/+
w25Tg/+ + MO2-ctnnb2

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Große et al., 2019 ZDB-PUB-190712-5 PMID:31290212

Zebrafish Wtx is a negative regulator of Wnt signaling but is dispensable for embryonic development and organ homeostasis

Große et al., 2019

ZDB-PUB-190712-5
PMID:31290212