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 (2024)

Publication Status: Submitted

Publication Type: Unpublished / Preprint

Future Publication Type: Journal article

Publication year: 2024

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 poorly understood. Using the developing Xenopus laevis brain as a model system, we identified a critical crosstalk between tissue stiffness and long-range 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 the brain parenchyma led to a decrease in the expression of the long-range chemical guidance cues Semaphorin3A (Sema3A) and Slit1, which instruct turning responses in distant cells. Furthermore, Piezo1 knockdown markedly reduced tissue stiffness. This tissue softening was independent of Sema3A depletion, and was caused by a decrease in the cell-cell adhesion proteins NCAM1 and N-Cadherin. Downregulating NCAM1 and N-Cadherin was sufficient to reduce tissue stiffness and Sema3A expression. Conversely, increasing environmental stiffness ex vivo resulted in enhanced tissue-level force generation and an increase in Slit1 and Sema3A expression. Moreover, stiffening soft brain regions in vivo induced ectopic Sema3A production via a Piezo1-dependent mechanism. Hence, tissue mechanics can locally modulate the availability of diffusive, long-range chemical signals, thus influencing cell function at sites distant from the mechanical cue. Such indirect regulatory mechanisms of cell function through mechanical signals are likely widespread across biological systems.

Authors with CRIS profile

Sudipta Mukherjee Lehrstuhl für Neuronale Mechanik Niklas Gampl Lehrstuhl für Neuronale Mechanik Ross McGinn Lehrstuhl für Medizinische Physik und Mikrogewebetechnik (IMP) Julia Becker Lehrstuhl für Neuronale Mechanik Kristian Franze Lehrstuhl für Neuronale Mechanik

Additional Organisation(s)

Sonderforschungsbereich 1540/1 - Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems

Involved external institutions

University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Pillai, E.K., Mukherjee, S., Gampl, N., McGinn, R., Mooslehner, K., Becker, J.,... Franze, K. (2026). 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. 2026.

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