Related Experiment Video

Updated: Jan 2, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

8.7K

Developmentally regulated Tcf7l2 splice variants mediate transcriptional repressor functions during eye formation

Rodrigo M Young1, Kenneth B Ewan2, Veronica P Ferrer1

  • 1Department of Cell and Developmental Biology, UCL, London, United Kingdom.

Elife
|December 13, 2019
PubMed

Insights

Tcf7l2 splicing regulates Wnt/β-Catenin signaling. Specific Tcf7l2 variants, including exon 5, are crucial for eye development by repressing Wnt pathway activity, interacting with Tle co-repressors.

Area of Science:

  • Developmental biology
  • Molecular genetics
  • Cancer research

Background:

  • Tcf7l2 is a key mediator of Wnt/β-Catenin signaling, influencing development, cancer, and type-2 diabetes.
  • The precise mechanisms governing Tcf7l2's diverse biological roles remain unclear.

Purpose of the Study:

  • Investigate the function of zebrafish tcf7l2 alternative splice variants.
  • Determine how specific tcf7l2 variants impact Wnt/β-Catenin signaling and embryonic development.

Main Methods:

  • Studied zebrafish tcf7l2 alternative splice variants.
  • Performed knockdown experiments in tcf7l1a mutants.
  • Utilized Wnt reporter assays to measure pathway activity.
  • Investigated interactions with Tle co-repressors.

Main Results:

  • Only tcf7l2 variants including exon 5 (or human analogs) effectively restore eye formation in tcf7l1a/tcf7l1b deficient embryos.
  • Knockdown of exon 5-specific tcf7l2 variants impairs eye development in tcf7l1a mutants.
  • Exon 5-containing tcf7l2 variants show potent repression of Wnt target gene promoters.
  • Repressive activity is linked to Tle co-repressor interaction and phosphorylation of exon 5 residues.

Conclusions:

  • Developmentally regulated splicing of tcf7l2 critically influences Wnt pathway transcriptional output.
  • Exon 5 inclusion in tcf7l2 variants is essential for repressor function and proper eye development.
  • Tcf7l2 splicing provides a mechanism to fine-tune Wnt signaling during embryogenesis.
Keywords:
alternative splicingdevelopmental biologyeye developmenttcf7l2zebrafish

More Related Videos

Dissection and Immunostaining of Imaginal Discs from Drosophila melanogaster10:10

Dissection and Immunostaining of Imaginal Discs from Drosophila melanogaster

Published on: September 20, 2014

27.5K
A Rapid In Vivo Bioassay for Developmentally Active Enhancers00:08

A Rapid In Vivo Bioassay for Developmentally Active Enhancers

1.4K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K
Master Transcription Regulators02:23

Master Transcription Regulators

2.7K
General Transcription Factors01:30

General Transcription Factors

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...
6.6K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
10.6K
Transcription Factors02:16

Transcription Factors

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...
82.1K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
25.6K