Related Experiment Video

Updated: Mar 10, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

2.0K

Tet proteins influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling

Xiang Li1,2, Xiaojing Yue1, William A Pastor1

  • 1Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.

Proceedings of the National Academy of Sciences of the United States of America
|December 9, 2016
PubMed

Insights

TET proteins regulate cell fate by influencing Wnt signaling. Loss of TET proteins impairs neural cell development and promotes cardiac mesoderm, highlighting their role in balancing cell differentiation.

Area of Science:

  • Epigenetics and Developmental Biology
  • DNA demethylation
  • Cell fate determination

Background:

  • TET-family dioxygenases modify DNA methylation, converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and oxidized forms.
  • These modifications are crucial for cellular differentiation and development.

Purpose of the Study:

  • To investigate the role of TET-family dioxygenases, particularly Tet3, in regulating cell fate decisions in mouse embryonic stem cells (mESCs) and embryos.
  • To elucidate the molecular mechanisms by which TET proteins control neural versus mesodermal cell fate.

Main Methods:

  • Utilized Tet3-deficient and Tet1/2/3-deficient mouse embryonic stem cells (mESCs).
  • Performed genome-wide analyses to assess DNA methylation and gene expression.
  • Examined Wnt signaling pathway activity and the expression of Wnt inhibitors like secreted frizzled-related protein 4 (Sfrp4).

Main Results:

  • Tet3 deficiency in mESCs impaired neural differentiation and promoted cardiac mesodermal fate.
  • Ectopic Tet3 expression enhanced neural differentiation and restricted cardiac mesoderm specification.
  • Tet1/2/3 deficiency led to hyperactivated Wnt signaling and aberrant differentiation of neuromesodermal progenitors (NMPs) towards mesoderm.
  • Tet3 was shown to inhibit Wnt signaling partly via Sfrp4 promoter demethylation and activation.

Conclusions:

  • TET proteins, especially Tet3, play a critical role in modulating Wnt signaling.
  • Proper balance between neural and mesodermal cell fate determination in mouse embryos and ESCs is established by TET proteins.
  • TET-mediated epigenetic regulation is essential for correct developmental trajectories.
Keywords:
DNA demethylationTET methylcytosine oxidasesWnt signalingmouse embryonic stem cellsneuromesodermal progenitors

More Related Videos

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions07:34

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions

Published on: February 16, 2017

8.4K
Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients08:10

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients

Published on: December 14, 2015

11.9K

Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.5K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.8K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.8K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.8K