Know thyself, Cell: Neuronal self-recognition

A neuron's shape is important for its function, but how does it get its shape in the first place? As we've discussed before, dendrites grow out of the cell body (soma) and follow a somewhat pre-described pattern.  A Purkinje cell always has a general corral-like shape, but each individual neuron is shaped a little differently.  (Just like an oak tree looks different from a pine tree, while at the same time no two oak trees are exactly the same.) 

branching tree at sunset, San Diego: taken by me

And just as trees branch and grow based on where the sunlight is coming from, dendrites can branch and grow depending on external factors.  Of course dendrites don't care about sunlight, but they do want to efficiently 'cover space' to receive lots of incoming signals. 

So how do they do it?

Some neurons have dendrites that repulse eachother. As in, if two dendrites are rooted to the same soma, those two dendrites will avoid eachother.  This is one way that the dendrite can 'cover space' very efficiently, it will branch and grow until it sees 'itself' and then it will stop and grow in a different direction. 


(source) The Leech: yuck.

In 1998, Wang and Macagno published a fascinating study using the mechanosensory neurons in the leech. These particular neurons show 'self-avoidance' (the dendrites of the same neuron do not overlap), but they don't show 'class-avoidance' (Dendrites from the same class of neurons do overlap).
Wang and Macagno wanted to test what exactly was so self-repulsive about these dendrites. 

There are two ways the cell could recognize itself:

1. Through the use of external signals (such as a chemical marker on the surface of the dendrites that sibling dendrites can detect)
2. Through the use of internal signals (such as the voltage activity transmitted within the cell)

To find out what method the dendrites are using to recognize themselves, Wang and Macagno used a laser to separate a small section of dendrite from the rest of the neuron.  Would the other dendrites still avoid this severed dendrite, or would they suddenly see it as a stranger and start to overlap with it?


Wang and Macagno, 1998 Figure 4

The attached dendrites start to treat the severed dendrite as a stranger, growing into its area and overlapping with it.  Figure 4 from Wang and Macagno shows the intact cell (A), the location of the cut (star in B), and the regrowth of both the severed dendrite and the still attached dendrite (arrow in D).

The authors offer several possible explanations for why a severed dendrite would appear to be a stranger to the rest of the dendrites, but all are speculative.  Maybe the electrical signal prevents gap junctions from forming. Maybe there are channels (such as NMDA receptors) that repulse each other when they are both active at the same time.  Maybe there is some cytoplasmic molecule that diffuses between the dendrites and prevents overlap (though the authors admit this mechanism sound too slow to do the job.)  The authors even find a problem with the electrical signal hypothesis in that:

"In some systems the blockade of electrical activity does not affect morphogenesis."

Since no one has tested a blockade of electrical activity on these neurons, the mechanism underlying the self-repulsive nature of these dendrites is still a mystery.
© TheCellularScale


Wang H, & Macagno ER (1998). A detached branch stops being recognized as self by other branches of a neuron. Journal of neurobiology, 35 (1), 53-64 PMID: 9552166