Eva Kreysing – Environmental stiffness regulates neuronal maturation via Piezo1-mediated TTR activity

Prof. Eva Kreysing, University of Warwick (UK)

Seminar Room 0.125, MPZPM, Kussmaulallee 2, 91054 Erlangen

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Abstract
During the development of the nervous system, neurons grow axons and dendrites to connect with other cells. As neurons become integrated into the neural network, they mature and develop electrical activity. While mechanical interactions between neurons and their environment are critical for axon growth and pathfinding, their role in the electrical maturation of neurons—and thus in the formation of circuits in the developing brain—remains poorly understood. Here, we identified environmental mechanics as a key regulator of neuronal maturation and dis-covered the pathway that links tissue mechanics to this process. Using electrophysiology, immunofluorescence, RNA sequencing, and CRISPR Cas9 knockdown in primary rat neurons, we showed that stiffer environments delay electrical maturation via Piezo1 activity, leading to down-regulation of transthyretin and delaying synaptogenesis and electrical maturation. In Xenopus laevis embryos, we found that tissue stiffness was negatively correlated with synapse density, and that stiffening of the brain significantly delays synaptic activity in vivo. Our findings highlight the critical role of mechanical signals in neuronal maturation and suggest that local brain tissue stiffness is a key regulator of circuit formation in the developing brain.

Biography
During my PhD in physics at RWTH Aachen and the Research Centre Jülich, I developed surface plasmon resonance microscopy (SPRM) to characterize the cell–substrate interface. I then joined the Franze Lab at Cambridge, where I studied how tissue mechanics regulate neuronal maturation via Piezo1 activity. In September 2025, I became an Assistant Professor at the University of Warwick, where my research focuses on how neurons sense the stiffness of their environment and how this shapes their development.

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