1. TLX, Wnt & neurogenesis

2. Neurogenesis
DeCarolis ‘10
Ables ‘10

3. Neurogenesis + Disease???
Major Depressive Disorder
Post Traumatic Stress Disorder
Alzheimer's
Schizophrenia

4. Wnt + neurogenesis
Well known in embryonic neural development

5. Wnt / β-catenin

6. In short…
Wnt
Extracellular ligand
Β-catenin
Transcription factor

7. Orphan Nuclear Receptor
TLX
Orphan Nuclear Receptor
??? Binds to it
“floats” in the nucleus and can act as a transcription factor
Also shown to be important in neural stem cell maintenance/renewal in adult & embryonic brains

8. Fig 1
Wnt Promoter
Wnt promoter reporter

9. ??? 1
TLX receptor
TLX 2
Wnt
Coding Region
Promoter
Wnt

10. TLX Wnt Β-catenin Cyclin D1 B-catenin reporter Fig 2 RT-PCR (RNA)
Block wnt transcrip
Fig 2
TLX
Wnt
Β-catenin
a = Bcatenin reporter, b = wnt siRNA
Cyclin D1
RT-PCR
(RNA)
Northern (RNA)
Western
(protein)

11. Fig 3 GSK P β-catenin β-catenin
Put neurons and wnt secreteing cells together, Tuji1=neurons, astrocytes=GFAP, oligodendrocytes=O4, DNA=DAPI

12. Fig 4
Frzb = wnt antagonist
A=western

13. Fig 5
BrdU =
fake thymidine
TLX
Wnt
Β-catenin
Cyclin D1
60%

14. Fig 6
TLX
Wnt
Β-catenin
DG=dentate, SVZ= subventricular zone
Cyclin D1

15. Fig 7
TLX
Wnt
Β-catenin
Cyclin D1

16. Wnt agonists as treatment for disease?
TLX/Wnt/Β-catenin – now implicated in ADULT:
Stem cell proliferation and renewal
Wnt agonists as treatment for disease?