@article{59e157fc2e5447fbb77d87c45e0993bc,
title = "Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling",
abstract = "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.",
keywords = "ERBB3, mTOR, neuregulin, neuronal-epithelial communication, organogenesis, specification, secretory, acinus",
author = "May, {Alison J} and Mattingly, {Aaron J} and Gaylord, {Eliza A} and Nathan Griffin and Sonia Sudiwala and Noel Cruz-Pacheco and Elaine Emmerson and Seayar Mohabbat and Sara Nathan and Hanan Sinada and Isabelle Lombaert and Knox, {Sarah M}",
note = "Funding Information: The authors thank Drs. Mathew Hoffman, Licia Selleri, Julie Sneddon, Susan Fisher, and Natalia Jura for providing guidance and critical reading on the manuscript. Funding was provided by the National Institutes of Health ( F31DE027607 [A.J. Mattingly], 5R01DE024188 [S.M.K.], and R35DE028255 [S.M.K.]) and the National Science Foundation ( 2014187660 [A.J. Mattingly]). Funding Information: The authors thank Drs. Mathew Hoffman, Licia Selleri, Julie Sneddon, Susan Fisher, and Natalia Jura for providing guidance and critical reading on the manuscript. Funding was provided by the National Institutes of Health (F31DE027607 [A.J. Mattingly], 5R01DE024188 [S.M.K.], and R35DE028255 [S.M.K.]) and the National Science Foundation (2014187660 [A.J. Mattingly]). A.J. May, A.J. Mattingly, I.M.A.L. and S.M.K. designed and planned the study. A.J. May, A.J. Mattingly, E.A.G. N.G. S.S. N.C.-P. E.E. S.M. S.N. H.S. I.M.A.L. and S.M.K. performed the experiments. A.J. May carried out scRNA-seq analysis. A.J. May and I.M.A.L. carried out RNA-seq analyses. A.J. May, A.J. Mattingly, I.M.A.L. and S.M.K. analyzed and interpreted the data. A.J. May created schematic illustrations. A.J. May, A.J. Mattingly, I.M.A.L. and S.M.K. prepared the manuscript. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location. One or more of the authors of this paper self-identifies as a gender minority in their field of research. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in their field of research. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = nov,
day = "21",
doi = "10.1016/j.devcel.2022.10.011",
language = "English",
volume = "57",
pages = "2550--2565.e5",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "22",
}