1. Downregulation of Wnt/ β -catenin signaling causes degeneration of hippocampal neurons in vivo April 1, 2011

2. Introduction  Wnt binds to Frizzled or other receptors such as LRP5/6  Downstream signaling cascade including Dvl, GSK-3 β, 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

4.  Two strains of transgenic mice:  Control Axin2P-rtTA  Ax2P-rtTA/TRE-Axin-EGFP

5. 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

6. April 1, 2011  Axin∆RGS (RGS domain of Axin deleted) Fig 1 B

7. April 1, 2011 Fig 1 C

8. April 1, 2011 Fig 1D TDBTN - Total Dendritic branching tip numbers

9. April 1, 2011  DMSO - Dissolves ICG- 001 and SP600125  ICG-001 – Inhibitor of Wnt signaling  SP600125 - Inhibitor of JNK Fig 2A

10. April 1, 2011

11. Fig 2B

12. April 1, 2011 Fig3A

13. April 1, 2011 Fig 3B - C

14. April 1, 2011

15. Fig 4A

16. April 1, 2011 Fig 4 B - C

17. April 1, 2011 Fig 4D

18. April 1, 2011 Fig 5A

19. April 1, 2011 Fig 5B - C

20. April 1, 2011 Fig 6

21. April 1, 2011 Fig 7 A - D

22. April 1, 2011 Fig 8 A-B

23. April 1, 2011 Fig 8 C

24. 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