Name: notch signaling in gut stem cell fate
Uploaded: 2023-04-30T12:47:37.000Z
Duration: 1 min 12 s
Channel: JoVE

In the intestinal epithelium, the Notch signaling pathway regulates cell fate under the influence of Wnt&#160; signaling.
Notch signaling helps maintain the intestinal stem cell or ISC pool in the intestinal crypt.
Here, the Notch ligands expressed on the Paneth cells interact with the Notch receptor on the ISCs and inhibit their differentiation, allowing the ISCs to maintain their stem-cell state in the crypt.
As the ISCs begin differentiation, the Notch signaling pathway also determines the fate of transit-amplifying, TA cells, which differentiate into either absorptive or secretory cell types.
Some TA cells express high levels of Notch ligands and prevent the differentiation of adjacent cells by activating their Notch receptors.
The Notch receptor-expressing TA cells keep dividing and move upward, away from the Wnt signals, before differentiating into absorptive cells.
In contrast, Notch ligand expressing TA cells stop dividing and differentiate into secretory cells. &#160;

role of notch signalling in intestinal stem cell renewal

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 known as trans-binding. In contrast, the signal is inhibited when the ligand binds to the same cell&#39;s receptor or cis-binding. During trans-activation, ADAM protease cleaves the extracellular region of the notch receptor, and &#947;-secretase cleaves the intracellular domain, also called the Notch intracellular domain (NICD), which translocates into the nucleus and activates the Hairy enhancer of split (Hes). Hes, in turn, inhibits Atoh1 and prevents Notch receptor cells from differentiating into secretory cells.
During tissue damage to the intestinal epithelium, the Paneth cells de-differentiate and replace the damaged cells via Notch signaling. Dysregulated Notch signals in the intestinal cells can cause various diseases. For example, mutations in Hes1 or Atoh1 can give rise to colorectal tumors. Reduced Notch signaling is linked to the rare inflammatory condition known as Celiac disease, which causes an allergic reaction when gluten is consumed. Therefore, targeting the Notch signaling pathway can be a therapeutic strategy for treating certain intestinal disorders.&#160;&#160;

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the ...

role-of-notch-signalling-in-intestinal-stem-cell-renewal

Education

JoVE Core

Cell Biology

Unit 1

Stem Cell Biology And Renewal in Epithelial Tissue

stem-cell-biology-and-renewal-in-epithelial-tissue

KEY TERMS AND CONCEPTS

notch signaling in gut stem cell fate

Notch signaling helps control how intestinal stem cells renew and decide what cell type to become. In the intestine, this pathway acts through Atoh1, also called atonal homolog 1. Atoh1 pushes cells to become secretory cells. When Notch signaling is active, it limits Atoh1 and keeps the stem cell pool balanced.

This pathway depends on direct contact between neighboring cells. It begins when a Notch ligand binds to a receptor on an adjacent cell, which is called trans-binding. If the ligand binds to the same cell’s receptor, or cis-binding, the signal is blocked. During trans-activation, ADAM protease cuts the outside part of the Notch receptor. Then γ-secretase cuts the inside part, known as the Notch intracellular domain or NICD.

The NICD moves into the nucleus and turns on Hairy enhancer of split, or Hes. Hes then suppresses Atoh1 and prevents Notch receptor cells from becoming secretory cells. During injury to the intestinal epithelium, Paneth cells can de-differentiate and replace damaged cells through Notch signaling. When this pathway is disrupted, it can contribute to disease. Mutations in Hes1 or Atoh1 can lead to colorectal tumors, and reduced Notch signaling is linked to celiac disease, a rare inflammatory condition that causes an allergic reaction to gluten. Because of these links, the Notch pathway is being studied as a possible target for treating some intestinal disorders.

Notch Signaling in Gut Stem Cell Fate

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Notch signaling helps control how intestinal stem cells renew and decide what cell type to become. In the intestine, this pathway acts through Atoh1, also called atonal homolog 1. Atoh1 pushes cells to become secretory cells. When Notch signaling is active, it limits Atoh1 and keeps the stem cell pool balanced. This pathway depends on direct contact between neighboring cells. It begins when a Notch ligand binds to a receptor on an adjacent cell, which is called trans-binding. If the ligand...

renewal of skin epidermal stem cells

Epidermal Cell Turnover and Repair

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key terms and concepts

Learn how Notch signaling controls intestinal stem cell renewal, blocks Atoh1, supports repair, and links to colorectal tumors and celiac disease.

Notch Signaling in Gut Stem Cell Fate | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Notch Signaling in Gut Stem Cell Fate

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