Gap Junctional Signaling in Pattern Regulation: Physiological network connectivity instructs growth and form

Keywords: gap junctions;networks;bioelectric;patterning;morphogenesis

Abstract
Gap junctions are aqueous channels that allow cells to communicate via physiological signals directly. The role of gap junctional connectivity in determining single-cell functions has long been recognized. However, gap junctions have another important role: the regulation of large-scale anatomical pattern. Gap junctions are not only versatile computational elements that allow cells to control which small molecule signals they receive and emit, but also establish connectivity patterns within large groups of cells. By dynamically regulating the topology of bioelectric networks in vivo, gap junctions underlie the ability of many tissues to implement complex morphogenesis. Here, we review recent data on patterning roles of gap junctions in growth of the zebrafish fin, the establishment of left-right patterning, the developmental dysregulation known as cancer, and the control of large-scale head-tail polarity and head shape in planarian regeneration. We propose a perspective in which gap junctions are not only molecular features functioning in single cells, but enable global neural-like dynamics in non-neural somatic tissues. This view suggests a rich program of future work which capitalizes on the rapid advances in the biophysics of gap junctions to exploit gap junction-mediated global dynamics for applications in birth defects, regenerative medicine, and morphogenetic bioengineering. This article is protected by copyright. All rights reserved.