A Ser252Trp substitution in mouse FGFR2 results in hyperplasia of embryonic salivary gland parenchyma

Watanabe, Tsukasa; Kometani-Gunjigake, Kaori; Nakao-Kuroishi, Kayoko; Ito-Sago, Misa; Mizuhara, Masahiro; Iwata, Daiki; Moriyama, Keiji; Ono, Kentaro; Kawamoto, T.

doi:10.1016/j.job.2021.02.008

Cited by 4 publications

(1 citation statement)

References 18 publications

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“…Reduced FGFR1b signaling, due to a hypomorphic mutation, leads to decreased branching morphogenesis and smaller glands 18 . Hypoplastic glands occur in Fgf10 +/- and Fgfr2b +/- mice 19 , 20 , while ligand-dependent-gain-of-function, due to an Fgfr2b mutation ( Fgfr2 +/Neo-S252W ) leads to hyperplasia 21 , 22 , suggesting sensitivity to FGF and FGFR protein expression levels. In addition, the SMGs of FGFR2c +/∆ hemizygous mice were hypoplastic, highlighting a role for mesenchymal FGF signaling, although this is not the focus of this investigation 23 .…”

Section: Introductionmentioning

confidence: 99%

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

Aure,

Symonds,

Villapudua

et al. 2023

Nat Commun

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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.

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Section: Introductionmentioning

confidence: 99%

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

Aure,

Symonds,

Villapudua

et al. 2023

Nat Commun

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Ser252Trp mutation in fibroblast growth factor receptor 2 promotes branching morphogenesis in mouse salivary glands

Iwata,

Kometani-Gunjigake,

Nakao-Kuroishi

et al. 2024

Journal of Oral Biosciences

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Salivary gland function, development, and regeneration

Chibly

Aure

Patel

et al. 2022

Physiological Reviews

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Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular and genetic levels; the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis and regeneration and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.

show abstract

A Ser252Trp substitution in mouse FGFR2 results in hyperplasia of embryonic salivary gland parenchyma

Cited by 4 publications

References 18 publications

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

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

Ser252Trp mutation in fibroblast growth factor receptor 2 promotes branching morphogenesis in mouse salivary glands

Salivary gland function, development, and regeneration

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