Epithelial tissue geometry directs emergence of bioelectric field and pattern of proliferation.

TitleEpithelial tissue geometry directs emergence of bioelectric field and pattern of proliferation.
Publication TypeJournal Article
Year of Publication2020
AuthorsSilver, BB, Wolf, AE, Lee, J, Pang, M-F, Nelson, CM
JournalMol Biol Cell
Date Published2020 Jul 21
KeywordsAnimals, Biomechanical Phenomena, Cell Line, Cell Nucleus, Cell Proliferation, Connexin 43, Electrophysiological Phenomena, Epithelial Cells, Epithelium, Membrane Potentials, Mice, Microtechnology, Models, Biological

<p>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.</p>

Alternate JournalMol Biol Cell
PubMed ID32520653
PubMed Central IDPMC7521849
Grant ListR01 CA187692 / CA / NCI NIH HHS / United States
R01 MH115750 / MH / NIMH NIH HHS / United States
U01 CA214292 / CA / NCI NIH HHS / United States