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How do axons find their way, or pathfind, during development? The stereotyped nerves contain the fasciculated axons of many neurons projecting from the CNS into the periphery AND axons of peripheral neurons projecting centrally. These many hundreds of growing axons sometimes join, sometimes part ways as they dance together through a constantly changing environment. How does this orchestrated patterning happen?

With our colleagues, the Johansen's at Iowa State, we discovered that the sensillar neurons (see project on leech vision) were the first to grow into the CNS and "pioneered" the MA nerve. Subsequently, developing neurons use these pioneer axons as a type of highway to find their way.

 

We also found at least 3 subsets of sensillar neurons, and were able to identify discrete molecular markers for them. These distinct subpopulations fasciculate together in the nerve, but once they enter the CNS they defasciculate and target different postsynaptic regions.

Stereoscopic micrographs of sensillar neurons and the 3-4 central fascicles.
 
To view using your binocular parallax, find a comfortable distance where you can focus upon the images. Then relax your eyes allowing them to cross a bit so you get a central image. The middle image should emerge as a 3-D view.

We used antibodies to isolate antigens associated with the different subpopulations of sensillar neurons. In this way we discovered a novel adhesion molecule as well as some that had a high degree of homology to known vertebrate neural adhesion molecules.

 

We also discovered that part of the conversation between these neurons involved all of them sharing a core protein that mediated homophilic adhesion (and fasciculation), but within the CNS subsets of neurons differentially glycosylated (added different carbohydrates) this core protein and this altered the adhesive properties, allowing these neurons to defasciculate and follow different off ramps to distinct destinations.

 

This molecular regulation remains a topic of intense interest.

Do fascicles represent functionally segregated inputs?

Now that we understand that there may be 3 different types of sensory response neurons in the sensilla, it is tempting to suggest that each type segregates within the CNS in different fascicles in order to contact different groups of postsynaptic partners.

 

In this scenario, one fascicle would be associated with tactile hairs (water wave detectors), one with UV light selective (mostly ventral) photoreceptors and the third with broadly tuned green selective (mostly dorsal) photoreceptors.

 

We are examining this hypothesis.

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