Related Experiment Video
Updated: May 10, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
BACE1 regulates hippocampal astrogenesis via the Jagged1-Notch pathway
Xiangyou Hu1, Wanxia He, Xiaoyang Luo
1Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Abstract:
BACE1 is the sole secretase for generating β-amyloid (Aβ) in vivo and is being actively pursued as a drug target for the treatment of Alzheimer's disease. Transmembrane BACE1 exerts its biological activity by cleaving its membrane-bound cellular substrates. Here, we reveal that BACE1 directly regulates the level of membrane-anchored full-length Jagged1 (Jag1), a signaling molecule important for the control of neurogenesis and astrogenesis, via interaction with its cognate Notch receptor. We show that shedding of Jag1 is reduced in BACE1 null mice and upregulated Jag1 enhances Notch signaling via cell-cell juxtacrine interactions. Additional biochemical assays confirmed that overexpression of BACE1 enhanced cleavage of Jag1. Consequently, BACE1 null mice exhibit a significant increase in astrogenesis with a corresponding decrease in neurogenesis in their hippocampi during early development. Hence, BACE1 appears to function as a signaling protease that controls the balance of neurogenesis and astrogenesis via the Jag1-Notch pathway.
Related Concept Videos
Hedgehog Signaling Pathway
Hedgehog Signaling Pathway
Notch Signaling Pathway
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 Pathway
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 Renewal
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...
TGF - β Signaling Pathway

