A new tool for tissue engineers: ions as regulators of morphogenesis during development and regeneration.

Currently, most of the research on how to encourage stem cells to replace missing tissues focuses on biochemical control, such as signaling by growth factors. In addition to basic questions, such as how are stem cells induced to differentiate into particular cell types, also inherent in those studies are practical questions about how to identify, grow, induce, and safely deliver stems cells to the proper target. At the Forsyth Center for Regenerative and Developmental Biology, we are examining a different set of signals, specifically bioelectric signals (the regulated movement of ions across membranes), including membrane voltage, pH, and gap junction activity and gating. We have found strong evidence that bioelectrical signals function at many critical, early points, both up- and downstream of transcriptional regulation, during the processes of normal morphogenesis and adult stem cell-based regeneration. Examples described include gap-junction-dependent regulation of stem cell identity in a flatworm, proton-flux-regulated establishment of left-right asymmetry in vertebrates, and proton-flux-initiated regeneration of a complex structure that includes spinal cord--the tadpole tail--in frogs.