Bio 3411 Lecture IV. Mechanisms of Neural Development

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Presentation transcript:

Bio 3411 Lecture IV. Mechanisms of Neural Development September 13, 2010 Cell Signaling Discovery of the Organizer How Could this Work? 4) The Answer 5) Blockers 6) Current View 7) Summary Inducers Antagonists September 13, 2010 Lecture IV. Mechanisms of Neural Development

Bio 3411 Lecture IV. Mechanisms of Neural Development September 13, 2010 Mangold –Spemann Experiments (1924) September 13, 2010 Lecture IV. Mechanisms of Neural Development

Bio 3411 Lecture IV. Mechanisms of Neural Development September 13, 2010 Cell Signaling Discovery of the Organizer How Could this Work? 4) The Answer 5) Blockers 6) Current View 7) Summary Inducers September 13, 2010 Lecture IV. Mechanisms of Neural Development

Inducing Neuronal Differentiation Observation: Animal Caps and neuronal cells (13) Models: slide 15 TGT-β (activin): (16) Pathway Experiment: Disrupted Pathway (18,19) Animal Cap -> Neurons (19) Model: Default? (21) BMP-4 -> TGT-β (20) Does BMP-4 play a role in neuroinduction? (21) Yes! BMP-4 induces diff. into epidermis (21)

Antagonists Chordin and Noggin exist (27) How do we know? Observations (28, 29) Chordin/Noggin/Follistatin interact (30)

Bio 3411 Lecture IV. Mechanisms of Neural Development September 13, 2010 Molecular Mechanism of Neuralization September 13, 2010 Lecture IV. Mechanisms of Neural Development

Bio 3411 Lecture IV. Mechanisms of Neural Development Neurogenesis: Inductive Mechanisms September 13, 2010 1. Neuroectodermal cells choose either a neuronal or epidermal fate. 2. Interactions between mesoderm and neuroectoderm induce neuroectoderm to adopt the neural fate. 3. Induction is signaled by Bone Morphogenic Protein-4 (BMP-4), a protein made and secreted by neuroectodermal cells. 4. BMP-4 inhibits neuralization and promotes the epidermal fate in neighboring cells. 5. Mesodermal cells secrete proteins (Chordin, Noggin, Follistatin) which directly bind and antagonizes BMP-4 activity. September 13, 2010 Lecture IV. Mechanisms of Neural Development

Bio 3411 Lecture IV. Mechanisms of Neural Development Neurogenesis: Inductive Mechanisms September 13, 2010 6. Neuroectodermal cells become neurons by suppression of BMP-4 activity by secreted antagonists from underlying mesodermal cells. 7. The “default” state of neuroectodermal cells is neuronal. 8. This mechanism is conserved between vertebrates and invertebrates. 9. BMP-4 is a member of the Transforming Growth Factor (TGF-b) family of signaling molecules. 10. Similar signaling events in the nervous system mediate changes in later development stages and in adult plasticity. September 13, 2010 Lecture IV. Mechanisms of Neural Development

NGF is the founding member of a large gene family of Neurotrophins (NTs), distantly related to insulin Mouse NGF Rabbit insulin NGF binds as a dimer to its receptor Wiesmann, C., et al. (1999) September 15, 2010 Lecture V. Cell Birth & Death

What’s the Point? Using the main point is explicit in the title Ask yourself what is the main point of this slide? What do I need to understand to get that point? How does this slide fit in with the lecture?