Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

9.2K
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...
9.2K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

2.2K
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...
2.2K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

7.6K
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...
7.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

2.3K
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.
2.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

2.8K
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...
2.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

GRP78 expression and prognostic significance in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant therapy versus surgery first.

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]·2021
Same author

Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies.

Clinical cancer research : an official journal of the American Association for Cancer Research·2021
Same author

Early detection of pancreatic cancer: current state and future opportunities.

Current opinion in gastroenterology·2021
Same author

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.

Nature communications·2021
Same author

Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis.

Thorax·2021
Same author

EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart.

Molecular cell·2021
Same journal

Feasibility of uniportal thoracoscopic sublobar resection without chest tube drainage: a retrospective cohort study.

Frontiers in oncology·2026
Same journal

Real-world effectiveness and safety of carfilzomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma: a retrospective analysis from China.

Frontiers in oncology·2026
Same journal

Caregiver satisfaction with early integrated palliative care in oncology: secondary outcomes from the PALLiON cluster-RCT.

Frontiers in oncology·2026
Same journal

Intracranial mesenchymal tumor with FET::CREB fusion: a rare case report.

Frontiers in oncology·2026
Same journal

The multifaceted roles of mitochondria and their therapeutic transformation: a new perspective on triple-negative breast cancer treatment.

Frontiers in oncology·2026
Same journal

Trastuzumab emtansine versus trastuzumab plus pertuzumab for HER2-positive breast cancer with residual disease after neoadjuvant therapy: a real-world study.

Frontiers in oncology·2026
See all related articles

Related Experiment Video

Updated: Oct 10, 2025

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

1.7K

HIF2 Regulates Intestinal Wnt5a Expression.

Carolina J García García1,2,3,4, Ariana C Acevedo Diaz5, Neeraj Kumari2,3

  • 1The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, United States.

Frontiers in Oncology
|December 13, 2021
PubMed
Summary
This summary is machine-generated.

Hypoxia-inducible factor 2 (HIF2) protects the gastrointestinal tract from radiation damage by increasing Wnt5a expression. This discovery offers a potential new strategy for mitigating radiation toxicity in patients undergoing abdominal radiation therapy.

Keywords:
GI radiotoxicityHIF2Wnt5ahypoxiaintestinal stem cellsradiotherapy

More Related Videos

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.4K
A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys
10:51

A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys

Published on: December 2, 2014

11.2K

Related Experiment Videos

Last Updated: Oct 10, 2025

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

1.7K
The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.4K
A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys
10:51

A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys

Published on: December 2, 2014

11.2K

Area of Science:

  • Oncology
  • Gastroenterology
  • Molecular Biology

Background:

  • Abdominal radiation therapy is limited by small intestine radiosensitivity.
  • No FDA-approved therapies exist to prevent gastrointestinal (GI) radiotoxicity.
  • Hypoxia-inducible factors (HIFs) regulate cell survival; HIF2 stabilization protects against GI radiotoxicity in mice.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which HIF2 confers GI radioprotection.
  • To investigate the role of Wnt5a in HIF2-mediated radioprotection.

Main Methods:

  • Developed mouse duodenal organoids and performed bulk RNA sequencing.
  • Overexpressed non-degradable HIF2 and analyzed gene expression.
  • Utilized luciferase reporter assays in human cells to assess promoter activity.
  • Evaluated crypt regeneration using spheroid formation assays and Wnt5a knockout models.

Main Results:

  • HIF2 upregulates genes involved in GI homeostasis, including Wnt5a.
  • HIF2 directly activates the WNT5A promoter via a hypoxia response element.
  • Pre-treatment with Wnt5a enhanced cryptogenic capacity post-irradiation.
  • Wnt5a knockout decreased intestinal stem cell radiogenic potential, which was rescued by Wnt5a treatment.

Conclusions:

  • HIF2-mediated GI radioprotection is dependent on the induction of Wnt5a expression.
  • Wnt5a is both necessary and sufficient for duodenal radioprotection.
  • Targeting the HIF2-Wnt5a pathway may offer a novel therapeutic strategy for mitigating GI radiotoxicity.