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TLX, Wnt & neurogenesis
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TLX, Wnt & neurogenesis

Jan 08, 2016

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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. - PowerPoint PPT Presentation
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Page 1: TLX, Wnt & neurogenesis

TLX, Wnt & neurogenesis

Page 2: TLX, Wnt & neurogenesis

DeCarolis ‘10 Ables ‘10

Neurogenesis

Page 3: TLX, Wnt & neurogenesis

Neurogenesis + Disease???Major Depressive DisorderPost Traumatic Stress DisorderAlzheimer'sSchizophrenia

Page 4: TLX, Wnt & neurogenesis

Wnt + neurogenesisWell known in embryonic neural

development

Page 5: TLX, Wnt & neurogenesis

Wnt / β-catenin

Page 6: TLX, Wnt & neurogenesis

Wnt

Β-catenin

Transcription factor

Extracellular ligand

In short…

Page 7: TLX, Wnt & neurogenesis

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

Page 8: TLX, Wnt & neurogenesis

Fig 1W

nt p

rom

ote

r re

porte

r

Wnt Promoter

Page 9: TLX, Wnt & neurogenesis

Coding Region

WntPromoter

???1

2

TLX

Wnt

Page 10: TLX, Wnt & neurogenesis

Fig 2

RT-PCR(RNA)

Northern (RNA)

Western(protein)

TLX

Wnt

Β-cateninCyclin

D1

B-catenin reporter Block wnt transcrip

Page 11: TLX, Wnt & neurogenesis

Fig 3

β-catenin

β-catenin

PGSK

Page 12: TLX, Wnt & neurogenesis

Fig 4

Frzb = wnt antagonist

Page 13: TLX, Wnt & neurogenesis

Fig 5

BrdU = fake

thymidine

60%

TLX

Wnt

Β-cateninCyclin

D1

Page 14: TLX, Wnt & neurogenesis

Fig 6

TLX

Wnt

Β-cateninCyclin

D1

Page 15: TLX, Wnt & neurogenesis

Fig 7

TLX

Wnt

Β-cateninCyclin

D1

Page 16: TLX, Wnt & neurogenesis

TLX/Wnt/Β-catenin – now implicated in ADULT:Stem cell proliferation and renewal

Wnt agonists as treatment for disease?