The Kolodkin lab's experiments in the invertebrate fruit fly central nervous system mirror related findings in the mouse reported Feb. 10, 2011 in Nature. Then, they showed that a different semaphorin cue is important for certain neurons to make precise connections within the developing inner plexiform layer of the retina, an elaborately laminated club-sandwich-like structure that must be precisely wired for accurate visual perception in mammals.
To demonstrate that semaphorins are necessary for neuronal projections from distinct classes of neurons to make their way to correct layers in this retinal "sandwich," the scientists examined the retinas of 3-, 7- and 10-day-old mice that were genetically modified to lack either a member of the semaphorin gene family or its appropriate plexin receptor. These mutants showed severe connectivity defects in one specific inner plexiform layer, revealing faulty neuronal targeting.
"In two distinct neural systems in flies and mammals, the same family of molecular guidance cues semaphorins and their receptors mediate targeting events that require exquisite short-range precision to generate complex neuronal connectivity," says Kolodkin who, as a postdoctoral fellow in the mid-1990s, first discovered the large family of semaphorin guidance cues working with the grasshopper nervous system.
"This work begins to tell us how, in a very small but highly ordered region of the nervous system, select target innervation and specific synaptic contacts between different classes of neurons can be established in the context of evolving circuit complexity" Kolodkin says.
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions