FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control

Axon guidance, a fundamental process in neural circuit formation, is intricately regulated by Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) through dynamic cytoskeletal remodeling. FGF signaling, mediated by heparan sulfate proteoglycans or Klotho co-factors, activates key downstream...

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Main Authors: Jiyuan Li, Hanqi Gao, Fang Liu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/11/777
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author Jiyuan Li
Hanqi Gao
Fang Liu
author_facet Jiyuan Li
Hanqi Gao
Fang Liu
author_sort Jiyuan Li
collection DOAJ
description Axon guidance, a fundamental process in neural circuit formation, is intricately regulated by Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) through dynamic cytoskeletal remodeling. FGF signaling, mediated by heparan sulfate proteoglycans or Klotho co-factors, activates key downstream pathways: PI3K-Akt, JAK-STAT, PLCγ, and RAS-MAPK. These pathways orchestrate actin filament dynamics, microtubule stability, and the organization of intermediate filaments. These pathways converge on Rho GTPases, cofilin, profilin, and tau to balance the cytoskeletal assembly−disassembly cycles, enabling growth cone navigation. Unresolved questions, such as the mechanisms underlying FGF-mediated growth cone steering, highlight critical future research directions. This review integrates structural, molecular, and functional insights into how FGF-FGFR interactions regulate axon pathfinding, emphasizing the crosstalk between signaling cascades and cytoskeletal plasticity. Elucidating these mechanisms not only advances our understanding of neural development but also opens therapeutic avenues for neuro-developmental disorders, nerve injury, and neurodegenerative diseases by targeting FGF-driven cytoskeletal dynamics.
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spelling doaj-art-8da62cb00b804bb7a3a84aa46dd59d172025-08-20T02:33:08ZengMDPI AGCells2073-44092025-05-01141177710.3390/cells14110777FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal ControlJiyuan Li0Hanqi Gao1Fang Liu2Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, ChinaQueen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, ChinaAxon guidance, a fundamental process in neural circuit formation, is intricately regulated by Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) through dynamic cytoskeletal remodeling. FGF signaling, mediated by heparan sulfate proteoglycans or Klotho co-factors, activates key downstream pathways: PI3K-Akt, JAK-STAT, PLCγ, and RAS-MAPK. These pathways orchestrate actin filament dynamics, microtubule stability, and the organization of intermediate filaments. These pathways converge on Rho GTPases, cofilin, profilin, and tau to balance the cytoskeletal assembly−disassembly cycles, enabling growth cone navigation. Unresolved questions, such as the mechanisms underlying FGF-mediated growth cone steering, highlight critical future research directions. This review integrates structural, molecular, and functional insights into how FGF-FGFR interactions regulate axon pathfinding, emphasizing the crosstalk between signaling cascades and cytoskeletal plasticity. Elucidating these mechanisms not only advances our understanding of neural development but also opens therapeutic avenues for neuro-developmental disorders, nerve injury, and neurodegenerative diseases by targeting FGF-driven cytoskeletal dynamics.https://www.mdpi.com/2073-4409/14/11/777axon guidancefibroblast growth factorsFGF signalingcytoskeleton
spellingShingle Jiyuan Li
Hanqi Gao
Fang Liu
FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control
Cells
axon guidance
fibroblast growth factors
FGF signaling
cytoskeleton
title FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control
title_full FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control
title_fullStr FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control
title_full_unstemmed FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control
title_short FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control
title_sort fgf mediated axon guidance role of downstream signaling pathways in cytoskeletal control
topic axon guidance
fibroblast growth factors
FGF signaling
cytoskeleton
url https://www.mdpi.com/2073-4409/14/11/777
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AT hanqigao fgfmediatedaxonguidanceroleofdownstreamsignalingpathwaysincytoskeletalcontrol
AT fangliu fgfmediatedaxonguidanceroleofdownstreamsignalingpathwaysincytoskeletalcontrol