Zipursky intitally discovered and explored the family of Dscam proteins – Oweing to much of our understandings of neuronal circuitry.
Tessier-Lavigne has been a name in my mind for six years now; he has uncovered many mechanisms relating to axon guidance. He has just been donned as Rockefeller University’s new president and has lead quite a wealthy career keeping up with basic research while also pursuing the biotech industry. He is definitely someone I look up to when I imagine life in terms of my own career. I welcome him to New York City in March 2011 (I’m hardly even an ant but still)!
Recently, He published in Journal of Neuroscience with Alexander Jaworski and Hua Long at Genentech on “Collaborative and Specialized Functions of Robo1 and Robo2 in Spinal Commissural Axon Guidance”.
Here are some main discoveries:
They analyzed the amount and ability of axons to cross the midline at the floor plate during project at E11.5 and E12.5 in various genetic backgrounds. Robo1 and Robo2 are the receptors which respond to the Slit1-3 repellants produced in the floor plate.
Robo3.1 is implicated in repressing Robo1’s function therefore diminishing axon repulsion and allowing commissural projecting cells to target their growth towards the floor plate. After midline crossing, Robo3.2 is then unregulated in axons and acts as a classic Slit repellent pushing axon growth towards its next target.Robo3 mutant animals have a major deficit in commissural projecting neurons in the spinal cord. In previous studies it was found that in the mutant Robo3 background loss of Robo1 partially rescued the deficit, as well as, loss of both Slit1 and Slit2.
In this study they found that in the Robo3 mutant background a loss of both Robo1 and Robo2 restored the crossing deficiency significantly. Indicating the failures of Commissural axons to project through the midline in the Robo3 mutant are partially due to Robo1-depedent repulsion but also Robo1- and Robo2-repulsion.
Due to combination mutants of Robo1/2/3 they end up illustrating that Robo1 and Robo2 work together to prevent post-crossing axons from reentering the midline and they have individualized roles in the sorting of axons into specific positions within the ventrolateral funiculus.
Lastly, I find most interesting, they provide evidence that there is most likely a Robo3-dependent mechanism not involving Robo1 or Robo2 (or the combination of both) allowing midline crossing in a subset of contralateral neurons.
I will post soon on the talks given at the Spencer award & lecture!
