The New Role of Morphogens in Axon Guidance
Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M. 2003. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell. 113(1): 11-23.
Briefly tell us a bit about yourself, your career path over the years, and specifically what led you to begin working on axon guidance. In an effort to bring us to the paper material, can you comment on whether it was specific data, intuition, or luck that made you suspect Shh was also acting as an axon guidance cue?
In the paper, you discussed the importance of a morphogen in axon guidance, in this case Shh. Is there any dose dependent response in axon guidance as there is in patterning?
The researchers discovered that Shh-mediated chemoattraction appears to require Smo function. This result was not anticipated however because there is no clear pathway from activated Smoothened to the cytoskeleton rearrangements required for growth cone turning. Is a pathway from activated Smoothened to the cytoskeleton being further investigated? Specifically, how does the intracellular machinery differ in commissural neurons to cause outgrowth in response to Netrin-1 and turning rather than outgrowth in response to Shh?
You mention that commissural axons project ventrally along the edge of the spinal cord until they reach the motor column. At that point, the axons change course slightly to project toward the ventral midline directly without tracing the edge. Of course the major attractant signals are Shh and Netrin-1, but what makes these axons alter direction slightly at the motor column so that the path does not continue around the edge of the spinal cord? Might it be intrinsic to the motor column, an increase in concentration of chemoattractants from the floor plate, or chemorepellents?
Shh is crucial along the midline axis of the spinal chord, but does it or other morphogens play a role in guiding commissural neurons to their correct targets other then the midline? Lastly, Netrin is a bifunctional cue, does Shh function alternatively as a repellent anywhere in the CNS?
As a senior neuroscience major trying to figure out my post graduation plans, I am very interested in learning more about careers in both academia and biotech companies. I was under the impression that one could either pursue a career in academia or industry; can you provide a little insight into how you are doing both? How are the research environments different? What, if any, suggestions do you give to someone trying to determine whether to go into biotech or academia?
Currently in your opinion what are the most pressing questions in the field of axon guidance, and what steps are you taking to address those questions?