Piezo1-mediated spontaneous calcium transients in satellite glia impact dorsal root ganglia development

Spontaneous Ca(2+) transients of neural cells is a hallmark of the developing nervous system. It is widely accepted that chemical signals, like neurotransmitters, contribute to spontaneous Ca(2+) transients in the nervous system. Here, we reveal an additional mechanism of spontaneous Ca(2+) transients that is mechanosensitive in the peripheral nervous system (PNS) using intravital imaging of growing dorsal root ganglia (DRG) in zebrafish embryos. GCaMP6s imaging shows that developing DRG satellite glia contain distinct spontaneous Ca(2+) transients, classified into simultaneous, isolated, and microdomains. Longitudinal analysis over days in development demonstrates that as DRG satellite glia become more synchronized, isolated Ca(2+) transients remain constant. Using a chemical screen, we identify that Ca(2+) transients in DRG glia are dependent on mechanical properties, which we confirmed using an experimental application of mechanical force. We find that isolated spontaneous Ca(2+) transients of the glia during development is altered by manipulation of mechanosensitive protein Piezo1, which is expressed in the developing ganglia. In contrast, simultaneous Ca(2+) transients of DRG satellite glia is not Piezo1-mediated, thus demonstrating that distinct mechanisms mediate subtypes of spontaneous Ca(2+) transients. 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 Ca(2+) transients in satellite glia and introduce mechanobiology as a critical component of spontaneous Ca(2+) transients in the developing PNS.