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TLX, Wnt & neurogenesis

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.

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TLX, Wnt & neurogenesis

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  1. TLX, Wnt & neurogenesis

  2. Neurogenesis DeCarolis ‘10 Ables ‘10

  3. Neurogenesis + Disease??? • Major Depressive Disorder • Post Traumatic Stress Disorder • Alzheimer's • Schizophrenia

  4. Wnt + neurogenesis • Well known in embryonic neural development

  5. Wnt / β-catenin

  6. In short… Wnt Extracellular ligand Β-catenin Transcription factor

  7. TLX OrphanNuclear 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

  8. Fig 1 Wnt Promoter Wnt promoter reporter

  9. ??? 1 TLX receptor TLX 2 Wnt Coding Region Promoter Wnt

  10. B-catenin reporter Block wnt transcrip Fig 2 TLX Wnt Β-catenin Cyclin D1 RT-PCR (RNA) Northern (RNA) Western (protein)

  11. Fig 3 β-catenin GSK P β-catenin

  12. Fig 4 Frzb = wnt antagonist

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

  14. Fig 6 TLX Wnt Β-catenin Cyclin D1

  15. Fig 7 TLX Wnt Β-catenin Cyclin D1

  16. TLX/Wnt/Β-catenin – now implicated in ADULT: • Stem cell proliferation and renewal • Wnt agonists as treatment for disease?

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