6 Sanes Ch 6.1 only 2009

6 Sanes Ch 6.1 only 2009 - Chapter 6 - part 1 Sanes, Reh...

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Chapter 6 - part 1 Sanes, Reh and Harris Target Selection: Getting axons to their proper target
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* Get off the beaten path Remain in the right structure Construct a map of the receptors Be true to your own layer Only synapse with the 'right' cells Challenges each axon faces in finding the right cell to synapse upon Axon Fascicle
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Defasciculation is regulated by molecules that decrease adhesion (like beat-1a) and leave the axon free to follow local guidance cues. (another ploy is to increase sialylation of NCAMs which decreases adhesion) “Beaten Path” was a mutant fly in which the motor axons didn’t de-fasciculate, and hence didn't make it to their proper target. Defasciculation is produced by the balance between the adhesion of beat-1c and the interference of beat-1a
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GENES IMPLICATED IN SNb AXON GUIDANCE (Cory Goodman Lab at Stanford): 1. Beaten Path (Beat) mutant 2. Fas II (expressed at high levels on motor neuron axons. 3. Connectin (large protein usually found in muscle) Fambrough, et al., Cell 87:1049-1058, 1996 anterior midline
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* Need mechanisms that attract axons to enter and form connections with target cells. Growth factors are important in this aspect of target selection.
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SNEAK PREVIEW: The neurotrophin family of growth factors is a Growth Factor peptide is a Tyrosine Kinase
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Target recognition usually requires that a molecule in the target organ activates a receptor on the growth cone Remember: the maxillary pad produces NGF and 70% of the sensory fibers have TrkA receptor on their growth cones. Targets can be: internal organs sensory cells striated muscles other neurons and in this case the epidermis and smooth muscle in hairs and blood vessels in the ear. SCG = Superior Cervical Ganglion: the anterior-most ganglion in the sympathetic chain NT3 Knockout
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Growth factors BDNF and NT-3 determine connections to the vestibular and cochlear subdivisions of the inner ear.
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Axons slow down and branch as they enter the target structure Control: retinal fibers slow upon entering tectum extra FGF2 prevents slowing How does this axonal branching occur?
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6 Sanes Ch 6.1 only 2009 - Chapter 6 - part 1 Sanes, Reh...

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