@ansuz @jonny yes it is at the cellular level. dunno about axons but dendrites, the tree-like structures that receive the inputs, have this - at least in the retina. am still not sure if this tilling is observed throughout the brain or only in sensory areas..

Haha, that's an interesting reframing @jonny ! Any useful concepts from cryptography we can import into neurobiology?

@manisha @ansuz
Re: Cell-type connections: clustered Protocadherin (cPcdh)-mediated self- and other-avoidance has been reported for dendrites in the retina and cerebellum, both regions where this tiling structure is required for the circuitry to function properly.

cPcdh randomization is controlled by epigentic modulation (histone methylation) ... (1/n)

@jonny @manisha @ansuz

... and one of the first things to go wrong when the 3D chromatin structure is disturbed, see e.g. here https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-022-01478-6
and here: https://academic.oup.com/nar/article/46/10/4950/4937548

It gets wilder in the cortex: There, cPcdhs regulate axon -> dendrite connection formation in a way that tracks how closely related the cells are.
The cortical plate has several generations of progenitors, each inheriting and partially remixing the cPcdh pattern. (2/n)

@jonny @manisha @ansuz

The final progenitor generation produces a set of a couple "sister cells" which preferentially form synapses with each other https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0326-6

In contrast, the less-related "cousin cells" set (likely to be direct surrounding neurons of the "sister cells") is contacted *less* than would be expected. This maintains a diversity of input processing, which is disrupted when cPcdh expression is artificially constrained: https://doi.org/10.1016/j.celrep.2023.112170

(3/n)

@jonny @manisha @ansuz

cPcdhs also seem to control where cortical neurons establish themselves in the cortex, i.e. how closely or far apart from their "sister cells" they settle before they make connections: https://www.nature.com/articles/s41586-022-05495-2#Abs1

So even though cPcdhs are not the only cell-surface molecules that control tiling/connectivity (that's a plausible hypothesis for each large family of signalling molecules), they by now have a relatively large body of evidence.

(4/n)