EBM Seminar Talk: Environmental stiffness regulates neuronal maturation via Piezo1-mediated TTR activity, Eva Kreysing (Warwick Medical School, University of Warwick, GB)

Environmental stiffness regulates neuronal maturation via Piezo1-mediated TTR activity
Prof. Eva Kreysing
Warwick Medical School, University of Warwick: Coventry, England, GB

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 discovered 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 downregulation of trans-thyretin 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.
More information: https://warwick.ac.uk/fac/sci/med/research/biomedical/labs/ekreysing/