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MCDB 4790 Axon Guidance The Chemoaffinity Hypothesis: Neurons make connec;ons with specific targets due to interac;ons with specific molecules. Roger Sperry 1913-­‐1994 • Shine a light on re;na, record electrical ac;vity from op;c tectum (the first place in the brain that neurons from the re;na make synapses) •  light on a cell in one part of the re;na always produced ac;vity in a cell in a par;cular part of the tectum • Inject a visible label into neurons •  an injected cell from the re;na always projected to a par;cular place in the tectum nasal temporal Nasal axons: posterior tectum Temporal axons: anterior tectum Dorsal axons: lateral tectum Ventral axons: medial tectum Target releases diffusible molecule in a gradient? Neighboring cells act as “signposts”? Specific molecules (breadcrumbs) present along the pathway? What was the hypothesis and how did they test it? M. Kuwajima Pronase is a mixture of several nonspecific endo-­‐ and exoproteases that digest proteins down to single amino acids. (Roche Applied Science) “Since treatment of posterior membranes alone is sufficient to change the preference of temporal axons so that they now grow on the formerly avoided membranes, it is likely that there is normally a repulsive substance in the posterior membranes which is selecUvely recognized by temporal axons and which is inacUvated by brief heat treatment.” How does their data support this (why not aQrac;on)? •  What actually guides axons? Tessier-­‐Lavigne and Goodman 1996 Receptors for Guidance Molecules Guidance ligands Tessier-­‐Lavigne and Goodman 1996