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Related Concept Videos

Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Analysis of Cardiomyocyte Development using Immunofluorescence in Embryonic Mouse Heart
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Isoform switch of T-cell factor7L2 during mouse heart development.

Bo Ye1,2, Lu Xiao3, Yuyong Xu1

  • 1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.

Journal of Molecular and Cellular Cardiology Plus
|June 16, 2025
PubMed
Summary

Alternative splicing of Tcf7l2 creates distinct protein isoforms that modulate WNT signaling in the heart during development and disease. A postnatal switch in Tcf7l2 isoforms may influence cardiomyocyte maturation.

Keywords:
Alternative splicingHeart developmentIsoformTcf7l2

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Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Gene Regulation

Background:

  • Canonical WNT signaling is crucial for heart development and disease, but its context-specific mechanisms are not fully understood.
  • Tcf7l2 (TCF/LEF transcription factor 7-like 2) is a key nuclear effector of WNT signaling, interacting with β-catenin.
  • Alternative splicing of Tcf7l2 transcripts is hypothesized to contribute to WNT signaling specificity in cardiac tissues.

Purpose of the Study:

  • To investigate the role of Tcf7l2 alternative splicing in mediating WNT signaling specificity within the developing and postnatal heart.
  • To identify and characterize different Tcf7l2 isoforms present in mouse ventricular tissues at embryonic and postnatal stages.

Main Methods:

  • Cloning and sequencing of Tcf7l2 transcripts from embryonic day 17.5 and postnatal day 8 mouse ventricular tissues.
  • Analysis of alternative splicing patterns, focusing on exon usage and variations in C-terminal exons.
  • Reverse transcription polymerase chain reaction (RT-PCR) to validate splicing patterns across multiple developmental stages.

Main Results:

  • Identification of 32 distinct Tcf7l2 isoforms from 53 sequenced transcripts, with significant variations in exon 4, 6, and 17 usage.
  • Alternative splicing was prominent in C-terminal exons (14, 15, 16), with exon 14 inclusion increasing significantly from embryonic to postnatal stages.
  • Exon 14 insertion created a redox-switch domain, and adenine indels near exon 18 altered isoform structures, affecting key functional motifs and driving isoform transitions (E, S, M).

Conclusions:

  • Tcf7l2 alternative splicing generates diverse protein isoforms with distinct functional domains, impacting WNT signaling pathways.
  • A postnatal, redox-sensitive switch in Tcf7l2 isoforms occurs, potentially regulating cardiomyocyte maturation.
  • These findings provide insights into the context-dependent mechanisms of WNT signaling in cardiac development and disease.