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Brain Power: Build It Francis Szele, PhD St. Annes College Physiology, Anatomy and Genetics University of Oxford [email_address] Nam et al., 2007 Magdalena Zernicka-Goetz Group
HOW TO BUILD A BRAIN
Stem cells give rise to the brain! ?
Three major classes of nerve cells Astrocytes Oligodendrocytes Neurons Glia
How Do We Know These Things?
Neurulation : The neural plate folds up to from the neural tube
Early ventricular zone contains many stem cells ,[object Object],[object Object]
The development of stem cells in the CNS ,[object Object],[object Object],[object Object]
Development of the Cerebral Cortex
JUST WHAT ARE  STEM CELLS?
Definition of Stem Cells ,[object Object],[object Object],[object Object],[object Object]
Stem cells - defying gravity?
iPSC - induced pluripotential stem cells ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Problems with iPSC’s ,[object Object],[object Object]
“ I NEED MORE NERVE CELLS, please”
The subventricular zone contains stem cell and migratory cells Granule neuron in olfactory bulb Nestin-eGFP Astrocytic stem cell Rapidly dividing progenitor Migrating neuroblasts Microglia Ependymal cells
Testing stems with neurospheres subdivide neurospheres:  stem cell self-renewal assays of secondary floating neurospheres,   stem cell fate potential assays of plated neurospheres,   assays of migration from plated neurospheres,  assays of cell surface molecule expression in plated neurospheres. day 8  in vitro Lesion Microdissect SVZ,  culture floating neurospheres 5 days day 7  in vitro Determine number and size of floating neurospheres +EGF/FGF2 Floating neurospheres Plated neurospheres astrocytes neurons oligodendrocytes
2 (multi)-photon time-lapse microscopy  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Integrated Microscopy Resource,  U. Wisconsin-Madison 2-photon confocal
Fluorescent mice to view stem cells and migration
4-dimensional quantification
Do Stem Cells Move? Is Dcx necessary for SVZ motility? Nestin-eGFP
Do Human Brains Have Stem Cells? Pinel, Biopsychology, 4th Ed. ,[object Object],[object Object],[object Object],Effects of Injury  Increased Proliferation Increased SVZ neurogenesis Some migration towards injury Very little survival and integration
Stem Cells to Treat Multiple Sclerosis
Conclusions ,[object Object],[object Object],[object Object],[object Object]

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Brain Power: Build It

  • 1. Brain Power: Build It Francis Szele, PhD St. Annes College Physiology, Anatomy and Genetics University of Oxford [email_address] Nam et al., 2007 Magdalena Zernicka-Goetz Group
  • 2. HOW TO BUILD A BRAIN
  • 3. Stem cells give rise to the brain! ?
  • 4. Three major classes of nerve cells Astrocytes Oligodendrocytes Neurons Glia
  • 5. How Do We Know These Things?
  • 6. Neurulation : The neural plate folds up to from the neural tube
  • 7.
  • 8.
  • 9. Development of the Cerebral Cortex
  • 10. JUST WHAT ARE STEM CELLS?
  • 11.
  • 12. Stem cells - defying gravity?
  • 13.
  • 14.
  • 15. “ I NEED MORE NERVE CELLS, please”
  • 16. The subventricular zone contains stem cell and migratory cells Granule neuron in olfactory bulb Nestin-eGFP Astrocytic stem cell Rapidly dividing progenitor Migrating neuroblasts Microglia Ependymal cells
  • 17. Testing stems with neurospheres subdivide neurospheres: stem cell self-renewal assays of secondary floating neurospheres, stem cell fate potential assays of plated neurospheres, assays of migration from plated neurospheres, assays of cell surface molecule expression in plated neurospheres. day 8 in vitro Lesion Microdissect SVZ, culture floating neurospheres 5 days day 7 in vitro Determine number and size of floating neurospheres +EGF/FGF2 Floating neurospheres Plated neurospheres astrocytes neurons oligodendrocytes
  • 18.
  • 19. Fluorescent mice to view stem cells and migration
  • 21. Do Stem Cells Move? Is Dcx necessary for SVZ motility? Nestin-eGFP
  • 22.
  • 23. Stem Cells to Treat Multiple Sclerosis
  • 24.

Editor's Notes

  1. Mouse 3.5 day embryo. Shown in yellow is the inner cell mass of the blastocyst - stem cells.
  2. Three major classes of cells in the nervous system
  3. The Neural plate folds up to from the neural tube Three basic layers during development; ectoderm, mesoderm, and endoderm. The nervous sytem is derived from the ectoderm. Neural tube gives rise to CNS. Neural crest gives rise to PNS: Neurons and glia of dorsal root and cranial ganglia, autonomic ganglia both sympathetic and parasympathetic, Schwann cells of the peripheral nervous system, adrenal medulla, melanocytes and other structures in the periphery.
  4. Much of what is known about cell migration in the brain has been through study of the cerebral cortex. The adult cerebral cortex is a 6 layered structure which forms through an unusual inside-out mode of migration. The bottom layers are formed first, and then the upper layers by cells moving through the bottom layers. Note that the E 8.5 ventricular zone is comprised of cells going through interkinetic nuclear migration (blue) and mitosis (green). Cells then migrate along radial glia to form the postmitotic layers. The first postmitotic layer is the preplate (PP). Then an intermediate zone (IZ) appears which is populated by incoming axons from more caudal structures. These axons may be a substrate for tangential migration. The Cajal-Retzius cells secrete reelin which inhibits neuronal migration of dorsally migrating cells and are responsible for cortical layerig. Later in development, a second layer of mitotically active cells, the subventricular zone (SVZ), appears (it should be called supra-ventricular zone because it is above the VZ). It is also termed the. Its cells are distinguishable from VZ because 1) they do not exhibit interkinetic movement of the nucleus and, 2) they go through the cell cycle at a slower rate.