Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling
| Autor: | 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 M.A. Lombaert, Sarah M. Knox |
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| Rok vydání: | 2022 |
| Předmět: |
secretory
Receptor ErbB-3 organogenesis Neuregulin-1 Biological Transport Cell Biology Mechanistic Target of Rapamycin Complex 2 Acinar Cells neuregulin General Biochemistry Genetics and Molecular Biology acinus Mice specification mTOR Humans Animals neuronal-epithelial communication ERBB3 Molecular Biology Developmental Biology Neuregulins Signal Transduction |
| Zdroj: | May, A J, Mattingly, A J, Gaylord, E A, Griffin, N, Sudiwala, S, Cruz-Pacheco, N, Emmerson, E, Mohabbat, S, Nathan, S, Sinada, H, Lombaert, I & Knox, S M 2022, ' Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling ', Developmental Cell, vol. 57, no. 22, pp. 2550-2565.e5 . https://doi.org/10.1016/j.devcel.2022.10.011 |
| ISSN: | 1878-1551 |
| DOI: | 10.1016/j.devcel.2022.10.011 |
| Popis: | Acinar cells are the principal secretory units 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) that regulate 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 murine 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 that NRG1-ERBB3 regulates each developmental program through an mTORC2 signaling pathway. Thus, we reveal that a neuronal-epithelial (NRG1/ERBB3/mTORC2) mechanism orchestrates the creation of functional acini. |
| Databáze: | OpenAIRE |
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