Downregulation of Wnt/β- catenin signaling causes degeneration of hippocampal neurons in vivo April 1, 2011
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Downregulation of Wnt/β-catenin signaling causes degeneration of hippocampal neurons in vivo
April 1, 2011
Introduction Wnt binds to Frizzled or other receptors such as
LRP5/6 Downstream signaling cascade including Dvl, GSK-3β,
Axin Accumulation of β-catenin enters nucleus and forms a
complex with Tcf/Lef This controls the expression of over a 100 genes Autism, Alzheimer's disease
AD patients with presenilin-1 mutation have low levels of β-catenin
LRP6 variations (influence Tcf/Lef reporter activity) associated with late onset AD
April 1, 2011
April 1, 2011
April 1, 2011
Two strains of transgenic mice: Control Axin2P-rtTA Ax2P-rtTA/TRE-Axin-EGFP
April 1, 2011
Inhibition of Wnt/β-catenin via Tet-On system of Axin expression
DOX to forms a complex with rtTA and binds to the TRE Turns on both GFP and the gene of interest (Axin)
Fig 1 A
April 1, 2011
Axin∆RGS (RGS domain of Axin deleted)
Fig 1 B
April 1, 2011
Fig 1 C
April 1, 2011
Fig 1D
TDBTN - Total Dendritic branching tip numbers
April 1, 2011
DMSO - Dissolves ICG-001 and SP600125
ICG-001 – Inhibitor of Wnt signaling
SP600125 - Inhibitor of JNK Fig 2A
April 1, 2011
April 1, 2011
Fig 2B
April 1, 2011
Fig3A
April 1, 2011
Fig 3B - C
April 1, 2011
April 1, 2011
Fig 4A
April 1, 2011
Fig 4 B - C
April 1, 2011
Fig 4D
April 1, 2011
Fig 5A
April 1, 2011
Fig 5B - C
April 1, 2011
Fig 6
April 1, 2011
Fig 7 A - D
April 1, 2011
Fig 8 A-B
April 1, 2011
Fig 8 C
Discussion Down-regulation of Wnt signaling causes
hippocampal neurodegeneration Ectopically expressed β-catenin and Dvl-1 did not
enhance arborization despite previous literature Yu and Malenka used stabilized form of β-catenin
while this study used wild type β-catenin Rosso tested for Dvl-1 at 2 DIV instead of at 4 and 9
DIVC. Decreased Wnt signaling may play a part in
anxiety responses exhibited in patients with dementia
April 1, 2011
Related Documents
