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
-
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/physiology*
- Animals
- Embryo, Nonmammalian
- Embryonic Development*
- Homeostasis*
- Mutant Proteins/pharmacology
- Regeneration
- Wnt Signaling Pathway/drug effects*
- Zebrafish
- PubMed
- 31290212 Full text @ Dev. Dyn.
Citation
Große, A., Perner, B., Naumann, U., Englert, C. (2019) Zebrafish Wtx is a negative regulator of Wnt signaling but is dispensable for embryonic development and organ homeostasis. Developmental Dynamics : an official publication of the American Association of Anatomists. 248(9):866-881.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping