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TLX, Wnt & neurogenesis
Neurogenesis
DeCarolis ‘10
Ables ‘10
Neurogenesis + Disease???
 Major Depressive Disorder
 Post Traumatic Stress Disorder
 Alzheimer's
 Schizophrenia
Wnt + neurogenesis
 Well known in embryonic neural development
Wnt / β-catenin
In short…
Wnt
Extracellular ligand
Β-catenin
Transcription factor
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
Fig 1
Wnt Promoter
Wnt promoter reporter
???
1
TLX
2
Wnt
Promoter
Coding Region
Wnt
B-catenin reporter
Block wnt transcrip
Fig 2
TLX
Wnt
Β-catenin
Cyclin D1
RT-PCR
(RNA)
Northern
(RNA)
Western
(protein)
Fig 3
β-catenin
GSK
P
β-catenin
Fig 4
Frzb = wnt antagonist
Fig 5
BrdU =
fake thymidine
TLX
Wnt
Β-catenin
Cyclin D1
60%
Fig 6
TLX
Wnt
Β-catenin
Cyclin D1
Fig 7
TLX
Wnt
Β-catenin
Cyclin D1
 TLX/Wnt/Β-catenin – now implicated in ADULT:
 Stem cell proliferation and renewal
 Wnt agonists as treatment for disease?