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

Notch Signaling Pathway03:14

Notch 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...
Notch Signaling Pathway03:14

Notch 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...
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...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Type IV Collagen of Basal Lamina01:05

Type IV Collagen of Basal Lamina

Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen  forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can exist in...
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...

You might also read

Related Articles

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

Sort by
Same author

Longitudinal GGT Trajectories Identify Prognostic Phenotypes in Paediatric Primary Sclerosing Cholangitis.

JHEP reports : innovation in hepatology·2026
Same author

Introducing new technology to your pediatric gastroenterology practice: Navigating the business side of healthcare.

Journal of pediatric gastroenterology and nutrition·2026
Same author

From supportive to targeted treatment strategies: the changing landscape of therapeutics in Alagille syndrome.

Expert opinion on therapeutic targets·2026
Same author

Improving the quality of paracentesis practices in people with advanced cirrhosis in an ambulatory care setting.

Journal of the Canadian Association of Gastroenterology·2026
Same author

Genomic Contributors to Congenital Diaphragmatic Hernia: Results of Exome Sequencing in 560 Probands and Cross Reference of Findings in an Independent Cohort.

American journal of medical genetics. Part A·2026
Same author

Expanding the Audiological Phenotype Associated With Activity-Dependent Neuroprotective Protein (ADNP) Syndrome: A Case Report and Literature Review Suggesting a Genotype/Phenotype Correlation.

American journal of medical genetics. Part A·2026

Related Experiment Video

Updated: May 26, 2026

Determining Bile Duct Density in the Mouse Liver
07:35

Determining Bile Duct Density in the Mouse Liver

Published on: April 30, 2019

NOTCH2 mutations in Alagille syndrome.

Binita Maya Kamath1, Robert C Bauer, Kathleen M Loomes

  • 1Division of Gastroenterology and Nutrition, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Canada.

Journal of Medical Genetics
|January 3, 2012
PubMed
Summary

Mutations in the NOTCH2 gene are a significant cause of Alagille syndrome (ALGS), beyond Jagged1 (JAG1) mutations. This study identified novel NOTCH2 mutations, expanding the known genetic causes of ALGS.

More Related Videos

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Related Experiment Videos

Last Updated: May 26, 2026

Determining Bile Duct Density in the Mouse Liver
07:35

Determining Bile Duct Density in the Mouse Liver

Published on: April 30, 2019

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Area of Science:

  • Genetics
  • Molecular Biology
  • Medical Genetics

Background:

  • Alagille syndrome (ALGS) is a multisystem disorder primarily caused by JAG1 gene mutations.
  • NOTCH2 gene mutations are rarely implicated in ALGS, with only two families previously reported.

Purpose of the Study:

  • To investigate the role of NOTCH2 mutations in patients with ALGS features but without JAG1 mutations.
  • To identify novel NOTCH2 mutations and characterize their associated clinical phenotypes.

Main Methods:

  • Screening of JAG1-negative individuals with ALGS features for NOTCH2 mutations.
  • Functional analysis of identified NOTCH2 mutations to assess their impact on Notch signaling.

Main Results:

  • Eight novel NOTCH2 mutations (six missense, one splicing, one nonsense) were identified in JAG1-negative patients.
  • Mutations affected both extracellular and intracellular domains, leading to decreased Notch signaling.
  • NOTCH2 mutations showed variable expressivity, with universal liver involvement and similar rates of ophthalmologic and renal anomalies compared to JAG1 mutations. Cardiac, vertebral, and facial feature involvement differed between the two groups.

Conclusions:

  • NOTCH2 is confirmed as a significant secondary disease gene for Alagille syndrome.
  • This study expands the spectrum of clinical phenotypes associated with NOTCH2 mutations in ALGS.