2. 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

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

4. 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

5. 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)

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

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

8. 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

9. 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

10. 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

11. 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?