Piezo1-mediated spontaneous activity of satellite glia impacts DRG development

Spontaneous activity of neural cells is a hallmark of the developing nervous system. It is widely accepted that chemical signals, like neurotransmitters, contribute to spontaneous activity in the nervous system. Here we reveal an additional mechanism of spontaneous activity that is mechanosensitive in the peripheral nervous system using intravital imaging of growing dorsal root ganglia (DRG) in zebrafish embryos. GCaMP6s imaging shows that developing DRG glia contain distinct spontaneous Ca2+ transients, classified into simultaneous, isolated and microdomains. Longitudinal analysis over days in development demonstrates that as DRG glia become more synchronized, isolated activity remains constant. Using a chemical screen, we identify that Ca2+ transients in DRG glia are dependent on mechanical properties, which we confirmed using an experimental application of mechanical force. We find that isolated spontaneous activity of the glia during development is altered by manipulation of mechanosensitive protein Piezo1, which is expressed in the developing ganglia. In contrast, simultaneous activity of DRG glia is not Piezo1-mediated, thus demonstrating that distinct mechanisms mediate subtypes of spontaneous activity. Activating Piezo1 eventually impacts the cell abundance of DRG cells and behaviors that are driven by DRG neurons. Together, our results reveal mechanistically distinct subtypes of Ca2+ transients in satellite glia and introduce mechanobiology as a critical component of spontaneous activity in the developing peripheral nervous system. ### Competing Interest Statement The authors have declared no competing interest.