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

Pillai, Eva K.; Mukherjee, Sudipta; Gampl, Niklas; McGinn, Ross J.; Mooslehner, Katrin A.; Becker, Julia; Winkel, Alexander K.; Thompson, Amelia J.; Franze, Kristian

doi:10.1038/s41563-025-02463-9

articleNature MaterialsJan 19, 2026HYBRID OA

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

EKEva K. Pillai SMSudipta Mukherjee NGNiklas Gampl RJRoss J. McGinn KAKatrin A. Mooslehner

European Bioinformatics Institute · University of Cambridge · +5 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Biological processes are regulated by chemical and mechanical signals, yet how these signalling modalities interact remains poorly understood. Here we identify a crosstalk between tissue stiffness and long-range chemical signalling in the developing Xenopus laevis brain. Targeted knockdown of the mechanosensitive ion channel Piezo1 in retinal ganglion cells or in the brain tissue surrounding retinal ganglion cells causes pathfinding errors in vivo. In the brain parenchyma, Piezo1 downregulation decreases the expression of the diffusive long-range chemical guidance cues Semaphorin3A (Sema3A) and Slit1, which instruct turning responses in distant cells. Furthermore, Piezo1 knockdown results in tissue softening…

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Topics & keywords

Topics

Keywords

SEMA3A
Mechanotransduction
Gene knockdown
Mechanosensitive channels
Downregulation and upregulation
Ex vivo
PIEZO1
In vivo

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