Epithelial tissue geometry directs emergence of bioelectric field and pattern of proliferation. Author Brian Silver, Abraham Wolf, Junuk Lee, Mei-Fong Pang, Celeste Nelson Publication Year 2020 Type Journal Article Abstract Patterns of proliferation are templated by both gradients of mechanical stress as well as by gradients in membrane voltage (Vm), which is defined as the electric potential difference between the cytoplasm and the extracellular medium. Either gradient could regulate the emergence of the other, or they could arise independently and synergistically affect proliferation within a tissue. Here, we examined the relationship between endogenous patterns of mechanical stress and the generation of bioelectric gradients in mammary epithelial tissues. We observed that the mechanical stress gradients in the tissues presaged gradients in both proliferation and depolarization, consistent with previous reports correlating depolarization with proliferation. Furthermore, disrupting the Vm gradient blocked the emergence of patterned proliferation. We found that the bioelectric gradient formed downstream of mechanical stresses within the tissues and depended on connexin-43 (Cx43) hemichannels, which opened preferentially in cells located in regions of high mechanical stress. Activation of Cx43 hemichannels was necessary for nuclear localization of Yap/Taz and induction of proliferation. Together, these results suggest that mechanotransduction triggers the formation of bioelectric gradients across a tissue, which are further translated into transcriptional changes that template patterns of growth. Keywords Animals, Mice, Biomechanical Phenomena, Models, Biological, Cell Line, Cell Proliferation, Cell Nucleus, Epithelium, Epithelial Cells, Membrane Potentials, Microtechnology, Connexin 43, Electrophysiological Phenomena Journal Mol Biol Cell Volume 31 Issue 16 Pages 1691-1702 Date Published 2020 Jul 21 ISSN Number 1939-4586 DOI 10.1091/mbc.E19-12-0719 Alternate Journal Mol Biol Cell PMCID PMC7521849 PMID 32520653 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML