tlx, wnt & neurogenesis. decarolis ‘10ables ‘10 neurogenesis

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TLX, Wnt & neurogenesis

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Page 1: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

TLX, Wnt & neurogenesis

Page 2: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

DeCarolis ‘10 Ables ‘10

Neurogenesis

Page 3: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

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

Page 4: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Wnt + neurogenesisWell known in embryonic neural

development

Page 5: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Wnt / β-catenin

Page 6: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Wnt

Β-catenin

Transcription factor

Extracellular ligand

In short…

Page 7: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 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. DeCarolis ‘10Ables ‘10 Neurogenesis

Fig 1W

nt p

rom

ote

r re

porte

r

Wnt Promoter

Page 9: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Coding Region

WntPromoter

???1

2

TLX

Wnt

Page 10: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 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. DeCarolis ‘10Ables ‘10 Neurogenesis

Fig 3

β-catenin

β-catenin

PGSK

Page 12: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Fig 4

Frzb = wnt antagonist

Page 13: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Fig 5

BrdU = fake

thymidine

60%

TLX

Wnt

Β-cateninCyclin

D1

Page 14: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Fig 6

TLX

Wnt

Β-cateninCyclin

D1

Page 15: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

Fig 7

TLX

Wnt

Β-cateninCyclin

D1

Page 16: TLX, Wnt & neurogenesis. DeCarolis ‘10Ables ‘10 Neurogenesis

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

Wnt agonists as treatment for disease?