Long-range chemical signallingin vivois regulated by mechanical signals

Pillai EK, Mukherjee S, Gampl N, McGinn R, Mooslehner K, Becker J, Thompson AJ, Franze K (2025)

Publication Status: Submitted

Publication Type: Unpublished / Preprint

Future Publication Type: Journal article

Publication year: 2025

DOI: 10.1101/2024.02.15.580459

Abstract

Biological processes are regulated by chemical and mechanical signals, yet the interaction between these signalling modalities remains unclear. Using the developing Xenopus laevis brain as a model system, we identified a critical crosstalk between tissue stiffness and chemical signalling in vivo. Targeted knockdown of the mechanosensitive ion channel Piezo1 in retinal ganglion cells (RGCs) led to pathfinding errors in vivo. However, pathfinding errors were also observed in RGCs expressing Piezo1, when Piezo1 was downregulated in the surrounding brain tissue. Depleting Piezo1 in brain parenchyma led to decreases in the expression of the long-range chemical guidance cues, Semaphorin3A and Slit1, and markedly reduced tissue stiffness. While tissue softening was independent of Sema3A depletion, Slit1 and Sema3A expression increased significantly in stiffer environments in vitro. Moreover, stiffening soft brain regions in vivo induced ectopic Sema3A production via a Piezo1-dependent mechanism. Our results demonstrate that brain tissue mechanics modulates the expression of key chemical signals, a likely phenomenon across diverse biological systems.

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

University of Cambridge United Kingdom (GB)

How to cite

APA:

Pillai, E.K., Mukherjee, S., Gampl, N., McGinn, R., Mooslehner, K., Becker, J.,... Franze, K. (2025). Long-range chemical signalling<i>in vivo</i>is regulated by mechanical signals. (Unpublished, Submitted).

MLA:

Pillai, Eva K., et al. Long-range chemical signalling<i>in vivo</i>is regulated by mechanical signals. Unpublished, Submitted. 2025.

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