Related Experiment Video
Updated: Jul 12, 2026
14:47
Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
Tadahiro Kitamura1, Yukari Ido Kitamura, Yasuhiro Funahashi
1Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
The Journal of Clinical Investigation
|August 25, 2007
Summary
Forkhead box O (Foxo) transcription factors interact with Notch signaling to control cell differentiation. This cooperation influences muscle fiber type and progenitor cell fate.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Forkhead box O (Foxo) transcription factors regulate metabolism and cellular differentiation.
- Mechanisms of Foxo-mediated cellular differentiation are not fully understood.
- Notch signaling activation mimics Foxo gain-of-function effects on differentiation.
Purpose of the Study:
- To investigate the mechanisms by which Foxo transcription factors regulate cellular differentiation.
- To explore the interaction between Foxo and Notch signaling pathways in muscle differentiation.
Main Methods:
- Utilized muscle differentiation as a model system.
- Investigated physical and functional interactions between Foxo and Notch.
- Examined the role of corepressor clearance from the Notch effector Csl.
- Assessed the impact of Foxo1 gain and loss of function on myogenesis.
- Analyzed conditional Foxo1 ablation in skeletal muscle.
Main Results:
- Foxo physically and functionally interacts with Notch signaling.
- Foxo promotes corepressor clearance from Csl, activating Notch target genes.
- Inhibition of Notch signaling partially rescues Foxo1-mediated inhibition of myoblast differentiation.
- Foxo1 loss of function prevents Notch-mediated inhibition of myogenesis and increases MyoD expression.
- Conditional Foxo1 ablation in skeletal muscle alters muscle fiber type distribution, favoring fast-twitch fibers.
Conclusions:
- Foxo and Notch signaling cooperate to regulate progenitor cell maintenance and differentiation.
- This cooperation integrates environmental cues (Notch) with metabolic cues (Foxo).
- The findings provide novel insights into the molecular mechanisms governing cell fate decisions.
More Related Videos
07:34The 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
08:06A Microfluidics Approach for the Functional Investigation of Signaling Oscillations Governing Somitogenesis
Published on: March 19, 2021
Related Concept Videos
03:14Notch 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 until 1985...
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 until 1985...
03:14Notch 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 until 1985...
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 until 1985...
01:13Formation of Muscle Fibers from Myoblasts
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
02:23Master 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...
01:12Role 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...
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...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...