Related Experiment Video

Updated: May 25, 2026

Generation, Maintenance, and Characterization of Human Pluripotent Stem Cell-derived Intestinal and Colonic Organoids
08:13

Generation, Maintenance, and Characterization of Human Pluripotent Stem Cell-derived Intestinal and Colonic Organoids

Published on: July 9, 2021

The role of Hes genes in intestinal development, homeostasis and tumor formation

Taro Ueo1, Itaru Imayoshi, Taeko Kobayashi

  • 1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.

Development (Cambridge, England)
|February 10, 2012
PubMed

Insights

Inactivating Hes genes in mice affects intestinal development and cell growth. Hes1 alone can reduce intestinal tumor cell proliferation and promote differentiation, suggesting it as a therapeutic target.

Area of Science:

  • Molecular biology
  • Developmental biology
  • Cancer research

Background:

  • Notch signaling is crucial for intestinal development, homeostasis, and tumorigenesis.
  • The precise downstream mechanisms of Notch signaling in the intestine are not fully understood.
  • Hes genes are known downstream effectors of Notch signaling.

Purpose of the Study:

  • To investigate the roles of Notch effectors Hes1, Hes3, and Hes5 in intestinal development and homeostasis.
  • To determine the potential of Hes1 as a therapeutic target for intestinal tumors.
  • To elucidate the cooperative function of Hes genes in the intestine.

Main Methods:

  • Inactivation of Notch effectors (Hes1, Hes3, Hes5) in adult mice.
  • Analysis of intestinal structures and cell proliferation.
  • Study of Apc mutation-induced intestinal tumors in mice.
  • Genetic redundancy analysis.

Main Results:

  • Inactivation of Hes1, Hes3, and Hes5 collectively reduced intestinal cell proliferation and increased secretory cell formation.
  • Hes1 inactivation alone was sufficient to reduce proliferation and induce differentiation of Apc-driven intestinal tumor cells.
  • Hes1 inactivation in tumors did not affect the homeostasis of normal intestinal crypts due to genetic redundancy.
  • Hes genes exhibit cooperative regulation of intestinal development and homeostasis.

Conclusions:

  • Hes genes function cooperatively to regulate intestinal development and homeostasis.
  • Hes1 is a potential therapeutic target for inducing differentiation of intestinal tumor cells.
  • Understanding Hes gene function provides insights into Notch signaling pathways in the intestine.

More Related Videos

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia08:14

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Published on: July 25, 2017

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation06:40

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation

Published on: April 1, 2021

Related Concept Videos

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...
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.
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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,...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...