Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease

  • Creighton T. Tuzon
  • Diana Rigueur
  • Amy E. MerrillEmail author
Skeletal Development (R Marcucio and J Feng, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Skeletal Development


Purpose of Review

Fibroblast growth factor receptor (FGFR) signaling regulates proliferation and differentiation during development and homeostasis. While membrane-bound FGFRs play a central role in these processes, the function of nuclear FGFRs is also critical. Here, we highlight mechanisms for nuclear FGFR translocation and the effects of nuclear FGFRs on skeletal development and disease.

Recent Findings

Full-length FGFRs, internalized by endocytosis, enter the nucleus through β-importin-dependent mechanisms that recognize the nuclear localization signal within FGFs. Alternatively, soluble FGFR intracellular fragments undergo nuclear translocation following their proteolytic release from the membrane. FGFRs enter the nucleus during the cellular transition between proliferation and differentiation. Once nuclear, FGFRs interact with chromatin remodelers to alter the epigenetic state and transcription of their target genes. Dysregulation of nuclear FGFR is linked to the etiology of congenital skeletal disorders and neoplastic transformation.


Revealing the activities of nuclear FGFR will advance our understanding of 20 congenital skeletal disorders caused by FGFR mutations, as well as FGFR-related cancers.


FGFR2 FGFR1 FGF2 Skeletal development Nuclear RTK, cancer 



The authors thank all the members of the Merrill laboratory for insightful discussions and, in particular, Lauren Bobzin for her critical review of this manuscript.

Funding Information

This work was supported by the National Institutes of Health R01DE025222 to A.E.M.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Right and Informed Consent

This article does not present any primary studies with human or animal subjects.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Creighton T. Tuzon
    • 1
  • Diana Rigueur
    • 1
  • Amy E. Merrill
    • 1
    • 2
    Email author
  1. 1.Center for Craniofacial Molecular Biology, Herman Ostrow School of DentistryUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of Biochemistry and Molecular Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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