Related Experiment Video

Updated: Apr 17, 2026

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models
07:48

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models

Published on: November 21, 2015

18.5K

TSC2/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium

Y Zhou1, P Rychahou2, Q Wang2

  • 1Markey Cancer Center, The University of Kentucky, Lexington, KY, USA.

Cell Death & Disease
|February 6, 2015
PubMed

Insights

Tuberous sclerosis 2 (TSC2) protein regulates intestinal cell differentiation. Its inactivation disrupts goblet and Paneth cell development by affecting mTORC1 and Notch signaling pathways, impacting gut homeostasis.

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Biology

Background:

  • Intestinal mucosa homeostasis relies on regulated cell proliferation, differentiation, and apoptosis.
  • Notch signaling is crucial for intestinal stem cell maintenance and differentiation.
  • Tuberous sclerosis 2 (TSC2) protein positively regulates MUC2 expression, a goblet cell differentiation marker.

Purpose of the Study:

  • To elucidate the role of TSC2 in intestinal epithelial differentiation.
  • To investigate the interplay between TSC2, mTORC1, and Notch signaling in regulating intestinal cell fate.

Main Methods:

  • Utilized transgenic mice expressing a dominant-negative TSC2 allele.
  • Administered Notch inhibitor dibenzazepine (DBZ) and mTORC1 inhibitor rapamycin.
  • Employed knockdown strategies for TSC2 and mTOR in the LS174T intestinal cell line.

Main Results:

  • TSC2 inactivation in mice increased mTORC1 and Notch activity, decreasing goblet and Paneth cell lineages.
  • DBZ and rapamycin treatments attenuated the differentiation defects caused by TSC2 inactivation.
  • TSC2 knockdown activated Notch signaling, while mTOR knockdown or rapamycin decreased it in LS174T cells.

Conclusions:

  • TSC2/mTORC1 signaling pathway is essential for maintaining intestinal epithelium homeostasis.
  • This pathway regulates intestinal cell differentiation by modulating Notch activity.

More Related Videos

Improved Swiss-rolling Technique for Intestinal Tissue Preparation for Immunohistochemical and Immunofluorescent Analyses07:42

Improved Swiss-rolling Technique for Intestinal Tissue Preparation for Immunohistochemical and Immunofluorescent Analyses

Published on: July 13, 2016

74.5K
Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids06:31

Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids

Published on: June 2, 2023

1.7K

Related Concept Videos

Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
3.7K
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
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
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
TGF - β Signaling Pathway01:16

TGF - 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...
11.1K