Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling.
Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling.
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DOI：
10.1016/j.devcel.2022.10.011
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发表时间：
2022-11-21
影响因子：
11.8
通讯作者：
Knox, Sarah M.
中科院分区：
文献类型：
--
作者：
May, Alison J.;Mattingly, Aaron J.;Gaylord, Eliza A.;Griffin, Nathan;Sudiwala, Sonia;Cruz-Pacheco, Noel;Emmerson, Elaine;Mohabbat, Seayar;Nathan, Sara;Sinada, Hanan;Lombaert, Isabelle M. A.;Knox, Sarah M.
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 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 NRG1-ERBB3 regulates each developmental program through an mTORC2 signaling pathway. Thus, we reveal a neuronal-epithelial (NRG1/ERBB3/mTORC2) mechanism to orchestrate the creation of functional acini. May and Mattingly et al. demonstrate that nerve-derived NRG1 activates ERBB3 enriched on acinar progenitors to drive acinar specification during salivary gland development. Specifically, they show that NRG1-ERBB3 regulates acinar lineage progression, polarization and secretion via mTORC2 to orchestrate the creation of functional acini.
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影响因子：
23.9
作者：
Brownell, Isaac;Guevara, Elizabeth;Bai, C. Brian;Loomis, Cynthia A.;Joyner, Alexandra L.
通讯作者：
Joyner, Alexandra L.
DOI：
10.1074/jbc.ra120.014960
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Beauchamp RL;Erdin S;Witt L;Jordan JT;Plotkin SR;Gusella JF;Ramesh V
通讯作者：
Ramesh V
影响因子：
5.3
作者：
Barrenschee M;Lange C;Cossais F;Egberts JH;Becker T;Wedel T;Böttner M
通讯作者：
Böttner M
影响因子：
4.8
作者：
El Soury M;Fornasari BE;Morano M;Grazio E;Ronchi G;Incarnato D;Giacobini M;Geuna S;Provero P;Gambarotta G
通讯作者：
Gambarotta G
影响因子：
2.7
作者：
Afelik, Solomon;Pool, Brandon;Jensen, Jan
通讯作者：
Jensen, Jan