Thanks, Elias!

I'd like to thank everyone who contributed to this tour de force, especially Eva and Sudi, our collaborators for their input (Christine Holt, @ben-fabry.bsky.social , @kevinchalut.bsky.social and many others), and our funders @erc.europa.eu @humboldt-foundation.de @dfg.de @wellcometrust.bsky.social

Accurate brain wiring is mechanochemical!
Environmental stiffness shapes chemical cues, and Piezo 1 tunes tissue mechanics via adhesions, controlling the expression of guidance cues in axon pathfinding.

Long-range chemical signalling in vivo is regulated by mechanical signals!

Building on our ex vivo results, we stiffened a local brain region – using sustained compression. This significantly increased Sema3A expression, showing that tissue mechanics instruct chemical guidance cues in vivo.

Is stiffness alone enough to change chemical guidance cues? Embedding soft brain regions in stiff 3D gels incresed levels of chemical guidance cues (using #HCRimaging) compared with soft 3D gels.

Lower N-cadherin and NCAM1 levels result in softer brains AND a decrease in Sema3A. Changing tissue stiffness seems to be enough to alter chemical guidance cue expression.

How does Piezo1 regulate brain #stiffness? Softening is not due to fewer cells, softer cells, or cytoskeletal changes. What changes is cell-cell #adhesion! Reducing Piezo1 decreases N-cadherin and NCAM1 (two major adhesion proteins).

Piezo1 regulates the mechanical landscape of the brain. Depleting it results in softer brain tissue (which isn’t just a consequence of decreasing chemical guidance cues).

Downregulating Piezo1 in the developing brain strongly reduces the expression of long-range chemical guidance cues, such as Semaphorin 3A (Sema3A) and Slit 1.
Piezo 1 isn’t just mechanical - it shapes the chemical landscape essential for long-range axon navigation.

🧠 In the developing #Xenopus brain, retinal ganglion axons follow a precise path to the optic tectum. Reducing #Piezo1, a mechanosensitive ion channel, in axons or surrounding tissues, result in axons stalling, wandering, or misrouting.

Thanks, Thomas! I really enjoyed my stay. Lots of good discussions with great people.