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

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

Fig 1 Wnt Promoter Wnt promoter reporter

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

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)

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

Fig 4 Frzb = wnt antagonist A=western

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

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

Fig 7 TLX Wnt Β-catenin Cyclin D1

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?