Endogenous bioelectric cues as morphogenetic signals in vivo

Complex pattern formation requires mechanisms to coordinate individual cell behavior towards the anatomical needs of the host organism. Alongside the well-studied biochemical and genetic signals functions an important and powerful system of bioelectrical communication. All cells, not just excitable nerve and muscle, utilize ion channels and pumps to drive standing gradients of ion content and transmembrane resting potential. In this chapter, we discuss the data that show that these bioelectrical properties are key determinants of cell migration, differentiation, and proliferation. We also highlight the evidence for spatio-temporal gradients of transmembrane voltage potential as an instructive cue that encodes positional information and organ identity, and thus regulates the creation and maintenance of large-scale shape. In a variety of model systems, it is now clear that bioelectric prepatterns function during embryonic development, organ regeneration, and cancer suppression. Moreover, genetic and pharmacological modulation of the prepatterns resident in physiological networks is a powerful modality for controlling growth and form. Recent data have revealed the mechanisms by which voltage gradients are transduced into downstream transcriptional cascades. Thus, mastery of the endogenous bioelectrical signaling pathways will have transformative implications for developmental biology, regenerative medicine, and synthetic bioengineering. Correspondence/Reprint request: Dr. Michael Levin, Center for Regenerative and Developmental Biology and Biology Department, Tufts University 200 Boston Ave. Suite 4600, Medford, MA 02155, e-mail: [email protected] Maria Lobikin & Michael Levin 284