Cargando…

FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation

Exocrine secretory 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...

Descripción completa

Detalles Bibliográficos
Autores principales: Aure, Marit H., Symonds, Jennifer M., Villapudua, Carlos U., Dodge, Joshua T., Werner, Sabine, Knosp, Wendy M., Hoffman, Matthew P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949235/
https://www.ncbi.nlm.nih.gov/pubmed/36824936
http://dx.doi.org/10.21203/rs.3.rs-2557484/v1
_version_ 1784892931720609792
author Aure, Marit H.
Symonds, Jennifer M.
Villapudua, Carlos U.
Dodge, Joshua T.
Werner, Sabine
Knosp, Wendy M.
Hoffman, Matthew P.
author_facet Aure, Marit H.
Symonds, Jennifer M.
Villapudua, Carlos U.
Dodge, Joshua T.
Werner, Sabine
Knosp, Wendy M.
Hoffman, Matthew P.
author_sort Aure, Marit H.
collection PubMed
description Exocrine secretory 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 epithelial SG populations later in development and during acinar differentiation are unknown. Here, we predicted FGFR dependence in specific populations using scRNAseq data and conditional mouse models to delete FGFRs in vivo. We identifed essential roles for FGFRs in craniofacial and early SG development, as well as progenitor function during duct homeostasis. Importantly, we discovered that FGFR2b was critical for seromucous and serous acinar cell differentiation and secretory gene expression (Bpifa2 and Lpo) via MAPK signaling, while FGFR1b was dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activated the FGFR2b-dependent seromucous transcriptional program. We propose a model where MEC-derived FGF7 drives seromucous acinar differentiaton, providing a rationale for targeting FGFR2b signaling in regenerative therapies to restore acinar function.
format Online
Article
Text
id pubmed-9949235
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Journal Experts
record_format MEDLINE/PubMed
spelling pubmed-99492352023-02-24 FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation Aure, Marit H. Symonds, Jennifer M. Villapudua, Carlos U. Dodge, Joshua T. Werner, Sabine Knosp, Wendy M. Hoffman, Matthew P. Res Sq Article Exocrine secretory 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 epithelial SG populations later in development and during acinar differentiation are unknown. Here, we predicted FGFR dependence in specific populations using scRNAseq data and conditional mouse models to delete FGFRs in vivo. We identifed essential roles for FGFRs in craniofacial and early SG development, as well as progenitor function during duct homeostasis. Importantly, we discovered that FGFR2b was critical for seromucous and serous acinar cell differentiation and secretory gene expression (Bpifa2 and Lpo) via MAPK signaling, while FGFR1b was dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activated the FGFR2b-dependent seromucous transcriptional program. We propose a model where MEC-derived FGF7 drives seromucous acinar differentiaton, providing a rationale for targeting FGFR2b signaling in regenerative therapies to restore acinar function. American Journal Experts 2023-02-16 /pmc/articles/PMC9949235/ /pubmed/36824936 http://dx.doi.org/10.21203/rs.3.rs-2557484/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Aure, Marit H.
Symonds, Jennifer M.
Villapudua, Carlos U.
Dodge, Joshua T.
Werner, Sabine
Knosp, Wendy M.
Hoffman, Matthew P.
FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_full FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_fullStr FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_full_unstemmed FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_short FGFR2b is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_sort fgfr2b is essential for salivary gland duct homeostasis and mapk-dependent seromucous acinar cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949235/
https://www.ncbi.nlm.nih.gov/pubmed/36824936
http://dx.doi.org/10.21203/rs.3.rs-2557484/v1
work_keys_str_mv AT auremarith fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation
AT symondsjenniferm fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation
AT villapuduacarlosu fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation
AT dodgejoshuat fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation
AT wernersabine fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation
AT knospwendym fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation
AT hoffmanmatthewp fgfr2bisessentialforsalivaryglandducthomeostasisandmapkdependentseromucousacinarcelldifferentiation