Conclusions and next steps
Endogenous bioelectrical states serve as instructive signals in patterning at multiple levels of organization, from single cells to the whole body plan. Vmem gradients specify information such as: initiating modules for complex self-limiting organogenesis (Adams et al., 2007b; Pai et al., 2015b), setting axial polarity (Beane et al., 2011; Durant et al., 2017; Levin, 2006; Oviedo et al., 2010; Stern and MacKenzie, 1983), serving as prepatterns for the layout of large regions (Adams et al., 2016; Pai et al., 2015a; Vandenberg et al., 2011), and even determining the shape and size of structures (Emmons-Bell et al., 2015; Perathoner et al., 2014). Despite the progress that has been made thus far, the field still faces a number of major questions. These include a more in depth understanding of the mechanisms by which cells compare bioelectric state across distances, elucidation of how bioelectric cues interface with chemical gradients and physical forces, and development of quantitative models of bioelectric circuits that are able to store patterning information needed to create complex structures. The ability of bioelectric signaling to direct cell behavior has been described in the literature for over a century, yet only recently are we gaining sufficient insight about mechanisms and global dynamics to enable biomedicine to unlock this valuable information. It is crucial to point out that continued advances in the control of regenerative patterning will require not only increase reductive detail on subcellular molecular pathways, but also integrative work to understand how large-scale pattern is established (and how growth is limited once appropriate anatomy has been restored) by large-scale bioelectrical circuits. Moving forward, researchers need to extend our knowledge about gene regulatory networks and signaling cascades to include information generated at the level of bioelectricity.
