Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling

Alison J May, Aaron J Mattingly, Eliza A Gaylord, Nathan Griffin, Sonia Sudiwala, Noel Cruz-Pacheco, Elaine Emmerson, Seayar Mohabbat, Sara Nathan, Hanan Sinada, Isabelle Lombaert, Sarah M Knox

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Acinar cells are the principal secretory unit of multiple exocrine organs. A single cell layered, lumenized acinus forms from a large cohort of epithelial progenitors that must initiate and coordinate three cellular programs of acinar specification, namely, lineage progression, secretion, and polarization. Despite this well-known outcome, the mechanism(s) regulating these complex programs are unknown. Here, we demonstrate that neuronal-epithelial cross-talk drives acinar specification through neuregulin (NRG1)-ERBB3-mTORC2 signaling. Using single-cell and global RNA-sequencing of developing salivary glands, we identified NRG1-ERBB3 to precisely overlap with acinar specification during gland development. Genetic deletion of Erbb3 prevented cell lineage progression and the establishment of lumenized, secretory acini. Conversely, NRG1 treatment of isolated epithelia was sufficient to recapitulate the development of secretory acini. Mechanistically, we found NRG1-ERBB3 regulates each developmental program through an mTORC2 signaling pathway. Thus, we reveal a novel neuronal-epithelial (NRG1/ERBB3/mTORC2) mechanism to orchestrate the creation of functional acini.
Original languageEnglish
Pages (from-to)2550-2565.e5
JournalDevelopmental Cell
Volume57
Issue number22
DOIs
Publication statusPublished - 21 Nov 2022

Keywords / Materials (for Non-textual outputs)

  • ERBB3
  • mTOR
  • neuregulin
  • neuronal-epithelial communication
  • organogenesis
  • specification
  • secretory
  • acinus

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