In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-07-03)
Abstract:
Adult neurogenesis in the hippocampus may represent a form of plasticity in brain functions including mood, learning and memory. However, mechanisms underlying neural stem/progenitor cells (NSPCs) proliferation are not well understood. We found that Agrin, a factor critical for neuromuscular junction formation, is elevated in the hippocampus of mice that are stimulated by enriched environment (EE). Genetic deletion of the Agrn gene in excitatory neurons decreases NSPCs proliferation and increases depressive-like behavior. Low-density lipoprotein receptor-related protein 4 (Lrp4), a receptor for Agrin, is expressed in hippocampal NSPCs and its mutation blocked basal as well as EE-induced NSPCs proliferation and maturation of newborn neurons. Finally, we show that Lrp4 interacts with and activates receptor tyrosine kinase-like orphan receptor 2 (Ror2); and Ror2 mutation impairs NSPCs proliferation. Together, these observations identify a role of Agrin-Lrp4-Ror2 signaling for adult neurogenesis, uncovering previously unexpected functions of Agrin and Lrp4 in the brain.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.45303.001
DOI:
10.7554/eLife.45303.002
DOI:
10.7554/eLife.45303.004
DOI:
10.7554/eLife.45303.005
DOI:
10.7554/eLife.45303.003
DOI:
10.7554/eLife.45303.006
DOI:
10.7554/eLife.45303.007
DOI:
10.7554/eLife.45303.010
DOI:
10.7554/eLife.45303.011
DOI:
10.7554/eLife.45303.012
DOI:
10.7554/eLife.45303.008
DOI:
10.7554/eLife.45303.009
DOI:
10.7554/eLife.45303.013
DOI:
10.7554/eLife.45303.016
DOI:
10.7554/eLife.45303.017
DOI:
10.7554/eLife.45303.018
DOI:
10.7554/eLife.45303.014
DOI:
10.7554/eLife.45303.015
DOI:
10.7554/eLife.45303.019
DOI:
10.7554/eLife.45303.021
DOI:
10.7554/eLife.45303.020
DOI:
10.7554/eLife.45303.022
DOI:
10.7554/eLife.45303.025
DOI:
10.7554/eLife.45303.026
DOI:
10.7554/eLife.45303.027
DOI:
10.7554/eLife.45303.023
DOI:
10.7554/eLife.45303.024
DOI:
10.7554/eLife.45303.028
DOI:
10.7554/eLife.45303.030
DOI:
10.7554/eLife.45303.031
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2019
detail.hit.zdb_id:
2687154-3