Getting from A to B

Rebrafish retinal cells, optic nerves, and glia are labeled. Retinal cells send projections through the optic nerve to their targets in the brain.Dr Kara Cerveny & Dr Steve Wilson Wellcome Images
Visual System of 4 day old zebrafish
Dr Kara Cerveny & Dr Steve Wilson Wellcome Images

How do individual cells find their way in the complex environment of a human body or a small worm? Some cells need to navigate from where they are born to where they are needed (like immune cells). Other cells need to send out a very long extension to make a contact with a very specific target (like a neuron sending an axon through layers and layers of other neurons to reach its connection in a circuit). I used to study a very specific example (one motor neuron connecting to one specific muscle) of this type of navigation in the fruit fly.

Nature Neuroscience recently published a groundbreaking axon guidance study stemming from collaboration between the Holt and Harris labs at the University of Cambridge. A great deal of research has uncovered a large number of signaling molecules and receptors that help neurons navigate to their target cells. It hasn’t been entirely clear how these signals actually result in the neurons physically changing course. This work in Nature Neuroscience shows evidence that when specific neurons (retinal ganglion cells) encounter a particular signal (Sema3A) while extending their axons they actually make an adhesion protein (NF-protocadherin) near the site where the axon encountered Sema3A. This changes how the neuron adheres to the local cells and this very localized differential in adhesion helps these neurons make a turn and continue to their target in the optic tectum.

This phenomenon requires very localized translation of the NF-protocadherin protein right at the site of contact with the instructive cue. This is one of the first examples that I’m aware of that A) proves local translation happens for a reason, B) shows local translation that occurs in response to a stimulus outside the cell. It’s also ground breaking for the field of axon guidance in that it begins to link cell-cell signaling to physical changes that occur in the responding cell.

I can’t wait to hear what other local changes occur as these cells navigate to their targets. I’m sure this system using NF-protocadherin is just one of the tools these cells are using.

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