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

Brian B. Silver, Abraham E. Wolf, Junuk Lee, Mei Fong Pang, Celeste M. Nelson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1691-1702
Number of pages12
JournalMolecular biology of the cell
Volume31
Issue number16
DOIs
StatePublished - Jul 21 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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