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Fibroblast growth factor signaling in axons: from development to disease

Cell Communication and Signaling, 2023 · DOI: https://doi.org/10.1186/s12964-023-01284-0 · Published: August 18, 2023

NeurologyGenetics

Simple Explanation

The fibroblast growth factor (FGF) family are polypeptides that act through four highly conserved transmembrane tyrosine kinase receptors to elicit a range of context-dependent tissue and cellular outcomes, including patterning, morphogenesis, migration, survival and differentiation. FGF signaling plays a vital role in a number of developmental and homeostatic processes. Dysfunction in its many players can lead to various human diseases, ranging from cancer to neurological conditions. Growing axons require proper guidance to accurately find their targets and establish the synaptic contacts that will define neural circuits. The central component of the axonal navigation system is the growth cone

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review

Key Findings

  • 1
    FGF2 promotes axonal elongation and branching in cultured DRGs neurons through activation of FGFR1.
  • 2
    FGF14 regulates the localization and currents of Nav and KCNQ channels in the AIS, while also regulating presynaptic Cav2.1 and Cav2.2 channels.
  • 3
    FGF22 promotes excitatory synapse formation in hippocampal neurons by increasing synaptic vesicle clustering.

Research Summary

This review discusses the role of the FGF system in axons, providing an original view of this multipurpose family of growth factors in nervous system (dys)function. The FGF family regulates nervous system development, axonal growth, synaptogenesis, and axonal regeneration, particularly after spinal cord injury. Dysregulation of the FGF system underlies several human neurological disorders. FGF signaling influences axonal development, regulates synapse formation, and contributes to post-injury remodeling of the spinal cord. Endogenous FGF signaling is involved in the regeneration of peripheral nerves and the spontaneous regeneration of the optic nerve and spinal cord in lower vertebrates.

Practical Implications

Therapeutic Potential for Spinal Cord Injury

Enhancing FGF signaling can promote the regrowth of injured axons in the damaged CNS, offering potential therapeutic strategies for spinal cord injury.

Understanding Neurological Disorders

Understanding the role of FGF dysfunction in axons may provide insights into the pathogenesis of human neurological diseases, potentially leading to new treatment approaches.

Targeted Drug Development

FGFs are critical regulators of synapse formation and maturation during post-injury remodeling of the spinal cord, implying that the developmental mechanisms that direct synapse formation in the CNS can be reactivated after injury.

Study Limitations

  • 1
    The mechanisms by which FGFs govern each step of axonal development remain largely unknown.
  • 2
    Elucidating the spatial and temporal expression/regulation of FGFs and their receptors during neurodevelopment.
  • 3
    Processes of FGF dysfunction in axons contributing to the pathogenesis of human diseases are only just beginning to be investigated.

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