Notch Signaling and Diseases

NewsGuard 100/100 Score

The notch signaling pathway plays a major role in regulating various cellular processes during development, therefore dysregulation of this pathway can lead to disease.

Notch signaling pathway. Image Credit: Ellepigrafica / Shutterstock
Notch signaling pathway. Image Credit: Ellepigrafica / Shutterstock

This basic signaling pathway has been used repeatedly in development, after initially being discovered in Drosophila. It has since been discovered that the notch signaling pathway is involved in multiple developmental processes, including hematopoiesis, somitogenesis, vasculogenesis, and neurogenesis.  Overall, it functions to influence downstream processes, including self-renewal process of stem-cell conservation, proliferation, specification of cell fate or differentiation, and apoptosis.

The Notch pathway is considered as a linear mechanism, where a ligand induces a receptor which subsequently results in transcriptional changes in the nucleus.  Mutations or altered signaling output in the pathway results in dysregulated Notch signaling, which is associated with many types of disease.

The Notch signaling pathway

Alagille Syndrome

Alagille syndrome (ALGS) is an autosomal dominant disorder. In this disorder, developmental abnormalities are observed in the liver, heart, eye, skeleton, and other organs. Neonatal jaundice and cholestasis are common in ALGS patients due to the lack of intrahepatic bile ducts.

Common features of ALGS are cardiac defects, skeletal defects, ophthalmological abnormalities, renal and pancreatic problems, and intracranial bleeding. Mutation in the JAG1 gene, which is a Notch signaling ligand, is the primary reason behind ALGS.
Prominent forehead, deep-set widely spaced eyes, a straight nose and pointed chin are the common facial characteristics of ALGS patients. Studies reported that Notch signaling is crucial for mid-face development.


CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a type of neurologic disorder. The common clinical manifestations of the affected individuals are migraine with aura, mood disorders, recurrent subcortical ischemic strokes, declined cognitive progress and dementia. The affected patients also exhibit premature death. Mutations in the NOTCH3 gene results in CADASIL.

Spondylocostal Dysostosis (SCD) and Spondylothoracic Dysostosis (STD)

Segmentation is essential for the development of vertebrate animals, and occurs through somitogenesis. The notch signaling pathway is a crucial regulator of this process. Spondylocostal Dysostosis (SCD) and Spondylothoracic Dysostosis (STD) are caused by mutations in genes encoding components of the notch signaling pathway. They are characterized by severe abnormalities in vertebrae and intercostal muscles. SCD and STD are categorized into abnormal vertebral segmentation (AVS) disorders.

Hajdu Cheney Syndrome

Mutations in the NOTCH 2 gene lead to the development of a rare condition called Hajdu-Cheney. The primary manifestations of this condition are focal bone destruction and osteoporosis. Other features of this condition include craniofacial abnormalities, renal cysts, cleft palate and cardiac defects.

Brain Tumors

Dysregulation of the Notch signaling pathway is associated with the development of human malignancies such as T-cell leukaemia, breast and colon related carcinomas, and cervical cancer. Recently, it was observed that Notch pathway plays a role in brain tumorigenesis. Expression of abnormal Notch ligand was observed from human tumors of glial origin in a recent study.

Retinal Dysplasia and Retina Vascular Homeostasis

In vertebrate, the retina plays a significant role in the vision pathway. Congenital blindness or vision disability occurs in individuals due to retinal dysplasia. Furthermore, neovascularization related diseases occur in adults because of adult retinal vascular homeostasis. Studies have also indicated that disruptions to the Notch signaling pathway could play a role in neural retina dysplasia and vascular abnormality.

Further Reading

Last Updated: Feb 26, 2019

Amrita Roy

Written by

Amrita Roy

Amrita is a freelance science and medical writer from India. She has a B.Sc. in Microbiology from the University of Calcutta, and holds a post graduation degree in Microbiology. Amrita loves to travel to various places. She enjoys cooking and has her own food blog where she shares easy and tasty recipes.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Roy, Amrita. (2019, February 26). Notch Signaling and Diseases. News-Medical. Retrieved on June 14, 2024 from

  • MLA

    Roy, Amrita. "Notch Signaling and Diseases". News-Medical. 14 June 2024. <>.

  • Chicago

    Roy, Amrita. "Notch Signaling and Diseases". News-Medical. (accessed June 14, 2024).

  • Harvard

    Roy, Amrita. 2019. Notch Signaling and Diseases. News-Medical, viewed 14 June 2024,


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.