Zebrafish Wtx is a negative regulator of Wnt signaling but is dispensable for embryonic development and organ homeostasis. Issue 9 (27th July 2019)

• Record Type: Journal Article
• Authors: Große, Andreas; Perner, Birgit; Naumann, Uta; Englert, Christoph
• Is Part Of: Developmental dynamics. Volume 248:Issue 9(2019)
• Page Start: 866
• Page End: 881
• Publication Date: 2019-07-27
• Subjects: Amer -- antisense morpholino -- TALENs -- Wilms tumor gene; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.84
• Languages: English
• ISSNs: 1058-8388

Abstract

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. Key Findings: Wtx knockdown causes patterning defects in early zebrafish embryogenesis. Mutation of zebrafish wtx is not associated with an obvious embryonic phenotype. Lack of compensation among the wtx/amer gene family. Triple wtx/amer2/amer3 mutants develop normally and are fertile.