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Published on: June 3, 2017
Identification and comparative expression analysis of a second wt1 gene in zebrafish
Frank Bollig1, Rebecca Mehringer, Birgit Perner
1Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Jena, Germany.
Abstract:
The Wilms' tumor suppressor gene wt1 encodes a zinc-finger transcription factor that plays an important role in the development of the mammalian genitourinary system. Mutations in WT1 in humans lead to anomalies of kidney and gonad development and cause Wilms' tumor, a pediatric kidney cancer. The inactivation of both wt1 alleles in mice gives rise to multiple organ defects, among them agenesis of kidney, spleen, and gonads. In zebrafish, an ortholog of wt1 has been described that is expressed in the pronephric field and is later restricted to the podocytes. Here, we report the existence of a second wt1 gene in zebrafish, which we have named wt1b (we named the initial gene wt1a). The overall sequence identity of the two Wt1 proteins is 70% and 92% between the zinc-finger regions, respectively. In contrast to wt1a, wt1b is expressed from the earliest stages of development onward, albeit at low levels. Both wt1a and wt1b are expressed in the intermediate mesoderm, with wt1b being restricted to a smaller area lying at the caudal end of the wt1a expression domain. In adult fish, high expression levels for both genes can be found in gonads, kidney, heart, spleen, and muscle.
Insights
Zebrafish possess two wt1 genes, wt1a and wt1b, crucial for genitourinary development. Discovering wt1b expands our understanding of kidney and gonad formation and Wilms' tumor gene regulation.
Area of Science:
- Developmental Biology
- Genetics
- Comparative Genomics
Background:
- The Wilms' tumor suppressor gene (WT1) is vital for mammalian genitourinary development.
- WT1 mutations cause kidney and gonad anomalies and pediatric kidney cancer (Wilms' tumor).
- A zebrafish WT1 ortholog (wt1a) is known, expressed in the pronephric field and podocytes.
Purpose of the Study:
- To identify and characterize a second WT1 gene in zebrafish.
- To investigate the expression patterns and conservation of zebrafish WT1 genes.
Main Methods:
- Bioinformatic analysis to identify the second gene.
- Sequence identity comparison between Wt1a and Wt1b proteins.
- Whole-mount in situ hybridization to determine expression domains.
Main Results:
- A second zebrafish wt1 gene, wt1b, was identified with 70% overall sequence identity to wt1a.
- Wt1b exhibits broader early expression than wt1a, with both genes present in the intermediate mesoderm.
- Both wt1a and wt1b show high expression in adult gonads, kidney, heart, spleen, and muscle.
Conclusions:
- Zebrafish possess two distinct wt1 genes (wt1a and wt1b) with conserved roles in development.
- Wt1b expression is broader in early development compared to wt1a.
- These findings contribute to understanding WT1 function in vertebrate development and disease.
