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ZFIN ID: ZDB-PUB-140712-2
Alternative splicing of Wilms tumor suppressor 1 (Wt1) exon 4 results in protein isoforms with different functions
Schnerwitzki, D., Perner, B., Hoppe, B., Pietsch, S., Mehringer, R., Hänel, F., Englert, C.
Date: 2014
Source: Developmental Biology   393(1): 24-32 (Journal)
Registered Authors: Englert, Christoph, Perner, Birgit
Keywords: Glomerulus, Kidney development, Morpholino, Pronephros, Transcription factor, Zebrafish
MeSH Terms:
  • Alternative Splicing/genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Cyprinodontiformes/embryology
  • Cyprinodontiformes/genetics
  • Fishes/abnormalities*
  • Fishes/genetics
  • Fundulidae/embryology
  • Fundulidae/genetics
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Kidney/abnormalities*
  • Molecular Sequence Data
  • Morpholinos/genetics
  • Oryzias/embryology
  • Oryzias/genetics
  • Poecilia/embryology
  • Poecilia/genetics
  • Pronephros/abnormalities*
  • Protein Isoforms/genetics
  • Protein Multimerization
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Two-Hybrid System Techniques
  • WT1 Proteins/genetics*
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed: 25014653 Full text @ Dev. Biol.
FIGURES
ABSTRACT
The Wilms tumor suppressor gene Wt1 encodes a zinc finger transcription factor that is essential for development of multiple organs including kidneys, gonads, spleen and heart. In mammals Wt1 comprises 10 exons with two characteristic splicing events: inclusion or skipping of exon 5 and alternative usage of two splice donor sites between exons 9 and 10. Most fish including zebrafish and medaka possess two wt1 paralogs, wt1a and wt1b, both lacking exon 5. Here we have characterized wt1 in guppy, platyfish and the short-lived African killifish Nothobranchius furzeri. All fish except zebrafish show alternative splicing of exon 4 of wt1a but not of wt1b with the wt1a(-exon 4) isoform being the predominant splice variant. With regard to function, Wt1a(+exon 4) showed less dimerization but stimulated transcription more effectively than the Wt1a(-exon 4) isoform. A specific knockdown of wt1a exon 4 in zebrafish was associated with anomalies in kidney development demonstrating a physiological function for Wt1a exon 4. Interestingly, alternative splicing of exon 4 seems to be an early evolutionary event as it is observed in the single wt1 gene of the sturgeon, a species that has not gone through teleost-specific genome duplication.
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