Open AccessThe developmental origins of Notch-driven intrahepatic bile duct disorders
Author(s) -
Anabel Martinez Lyons,
Luke Boulter
Publication year - 2021
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.327
H-Index - 83
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.048413
Subject(s) - notch signaling pathway , biology , intrahepatic bile ducts , progenitor cell , embryonic stem cell , cell fate determination , alagille syndrome , microbiology and biotechnology , bile duct , stem cell , cholestasis , signal transduction , cancer research , medicine , endocrinology , genetics , gene , transcription factor
The Notch signaling pathway is an evolutionarily conserved mechanism of cell-cell communication that mediates cellular proliferation, cell fate specification, and maintenance of stem and progenitor cell populations. In the vertebrate liver, an absence of Notch signaling results in failure to form bile ducts, a complex tubular network that radiates throughout the liver, which, in healthy individuals, transports bile from the liver into the bowel. Loss of a functional biliary network through congenital malformations during development results in cholestasis and necessitates liver transplantation. Here, we examine to what extent Notch signaling is necessary throughout embryonic life to initiate the proliferation and specification of biliary cells and concentrate on the animal and human models that have been used to define how perturbations in this signaling pathway result in developmental liver disorders.