91福利

Abstract: During development, cells are highly dynamic and respond to a plethora of chemical and mechanical signal in their environment. During brain morphogenesis, for example, neurons extend axons over large distances along well-defined pathways. How these axons are formed is currently poorly understood, and once initiated, how axons know where to grow and connect is also still an open question. Axon pathfinding is regulated by both gradients of chemical guidance cues and gradients in tissue stiffness. However, we currently know very little about how these signals interact. Using a combination of ex vivo and in vivo approaches, we identified the mechanosensitive ion channel Piezo1 as a key integrator of chemical and mechanical signals. Downregulation of Piezo1 in the brain parenchyma surrounding healthy growing axons led to aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors. We found a decrease in both the chemical guidance cues Semaphorin3A and Slit1 and brain stiffness. While the stiffness of cells was unaffected, cell-cell adhesion was significantly reduced, leading to a fluidization of the tissue. While a decrease in chemical guidance cues did not lead to tissue softening, tissue softening led to a decrease in guidance cues. Hence, tissue stiffness not only directly impacts neuronal growth but also indirectly by regulating the availability of long-range chemical guidance cues far away from the actual mechanical signal in the surrounding tissue. Our data thus strongly indicate that chemical and mechanical signaling pathways are intimately linked, and that their interaction is crucial for morphogenetic events.

Biography: Kristian Franze qualified as a Veterinarian at the University of Leipzig in Germany, where he also obtained a PhD in Physics in 2007. After a postdoc at the Cavendish Laboratory of the University of Cambridge, UK, he started his lab in 2011 at the Department of Physiology, Development and Neuroscience in Cambridge. Kristian received several awards for his work, including an MRC Career Development Award, an HFSP Young Investigator Award, an ERC Consolidator Award, and an ERC Synergy Grant. In 2020, he obtained an Alexander von Humboldt-Professorship to become the Director of the Medical Institute of Biophysics at FAU and of the newly founded Max Planck Zentrum f眉r Physik und Medizin in Erlangen, Germany. The research of his lab focuses on how mechanical signals, such as cellular forces or tissue stiffness, contribute to regulating the development and regeneration of the nervous system.