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

TLX, Wnt & neurogenesis

DeCarolis ‘10 Ables ‘10

Neurogenesis

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

Wnt + neurogenesisWell known in embryonic neural

development

Wnt / β-catenin

Wnt

Β-catenin

Transcription factor

Extracellular ligand

In short…

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 1W

nt p

rom

ote

r re

porte

r

Wnt Promoter

Coding Region

WntPromoter

???1

2

TLX

Wnt

Fig 2

RT-PCR(RNA)

Northern (RNA)

Western(protein)

TLX

Wnt

Β-cateninCyclin

D1

B-catenin reporter Block wnt transcrip

Fig 3

β-catenin

β-catenin

PGSK

Fig 4

Frzb = wnt antagonist

Fig 5

BrdU = fake

thymidine

60%

TLX

Wnt

Β-cateninCyclin

D1

Fig 6

TLX

Wnt

Β-cateninCyclin

D1

Fig 7

TLX

Wnt

Β-cateninCyclin

D1

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

Wnt agonists as treatment for disease?