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FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation

Author

Listed:
  • Marit H. Aure

    (National Institutes of Health)

  • Jennifer M. Symonds

    (National Institutes of Health)

  • Carlos U. Villapudua

    (National Institutes of Health)

  • Joshua T. Dodge

    (National Institutes of Health)

  • Sabine Werner

    (Swiss Federal Institute of Technology (ETH))

  • Wendy M. Knosp

    (National Institutes of Health)

  • Matthew P. Hoffman

    (National Institutes of Health)

Abstract

Exocrine acinar cells in salivary glands (SG) are critical for oral health and loss of functional acinar cells is a major clinical challenge. Fibroblast growth factor receptors (FGFR) are essential for early development of multiple organs, including SG. However, the role of FGFR signaling in specific populations later in development and during acinar differentiation are unknown. Here, we use scRNAseq and conditional deletion of murine FGFRs in vivo to identify essential roles for FGFRs in craniofacial, early SG development and progenitor function during duct homeostasis. Importantly, we also discover that FGFR2 via MAPK signaling is critical for seromucous acinar differentiation and secretory gene expression, while FGFR1 is dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activates the FGFR2-dependent seromucous transcriptional program. Here, we propose a model where MEC-derived FGF7 drives seromucous acinar differentiation, providing a rationale for targeting FGFR2 signaling in regenerative therapies to restore acinar function.

Suggested Citation

  • Marit H. Aure & Jennifer M. Symonds & Carlos U. Villapudua & Joshua T. Dodge & Sabine Werner & Wendy M. Knosp & Matthew P. Hoffman, 2023. "FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42243-0
    DOI: 10.1038/s41467-023-42243-0
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    References listed on IDEAS

    as
    1. Jeong Mi Kim & Mi Eun Choi & Seok-Ki Kim & Ji Won Kim & Young-Mo Kim & Jeong-Seok Choi, 2020. "Keratinocyte Growth Factor-1 Protects Radioiodine-Induced Salivary Gland Dysfunction in Mice," IJERPH, MDPI, vol. 17(17), pages 1-9, August.
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    Cited by:

    1. Vaishali N. Patel & Marit H. Aure & Sophie H. Choi & James R. Ball & Ethan D. Lane & Zhangjie Wang & Yongmei Xu & Changyu Zheng & Xibao Liu & Daniel Martin & Jillian Y. Pailin & Michaela Prochazkova &, 2024. "Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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