Temporal tuning of actin nucleation by the repurposed DNA repair complex RAD51/fignl1 encodes distinct axon guidance decisions
Abstract
Axon guidance is essential for neural circuit assembly and function. While much of the repertoire of guidance cues and receptors is known, its limited diversity cannot fully explain the remarkable complexity of the brain connectome. How temporally ordered, context-dependent intrinsic programs shape the diversity of axonal responses to guidance signals remains poorly understood. We reveal how non-canonical Wnt5a signalling repurposes the DNA repair complex RAD51/fignl1 as a downstream integrator to control retinal ganglion cell axon decision-making at the midline. We demonstrate that differential RAD51/fignl1 expression and interaction dynamics between ipsilateral and contralateral axons tunes the magnitude and temporal dynamics of F-actin nucleation, thereby encoding their trajectory choice. Our findings establish temporal control of cytoskeletal dynamics as a key determinant of axon decision-making and thereby a fundamental layer of circuit wiring. They provide a potential mechanistic framework linking mutations in the DNA repair gene RAD51 to neurodevelopmental disorders with midline guidance defects.
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BibTeX
@misc{zerkoune2026temporal,
title = {{Temporal tuning of actin nucleation by the repurposed DNA repair complex RAD51/fignl1 encodes distinct axon guidance decisions}},
author = {Samya Zerkoune and Yvrick Zagar and Julie Delaroche and Julia Danicka and Juliette Vougny and Sinthuya Uthayasuthan and Julien Aureille and Fiona Roche and Rhanna Haanjtes and Claudia Gomez-Bravo and Sarah Baudet and Eric Denarier and Akbar Zainu and Philippe Bun and Xavier Guillonneau and Anne Debant and Frédéric Baudat and Xavier Nicol and Nicolas Pietrancosta and Jérôme Boudeau and Annie Andrieux and Isabelle Arnal and Adrien Antkowiak and Fassier Coralie},
howpublished = {HAL},
year = {2026},
month = oct,
doi = {10.64898/2026.10.17.759799},
url = {https://hal.science/hal-05843590v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Temporal tuning of actin nucleation by the repurposed DNA repair complex RAD51/fignl1 encodes distinct axon guidance decisions
AU - Samya Zerkoune
AU - Yvrick Zagar
AU - Julie Delaroche
AU - Julia Danicka
AU - Juliette Vougny
AU - Sinthuya Uthayasuthan
AU - Julien Aureille
AU - Fiona Roche
AU - Rhanna Haanjtes
AU - Claudia Gomez-Bravo
AU - Sarah Baudet
AU - Eric Denarier
AU - Akbar Zainu
AU - Philippe Bun
AU - Xavier Guillonneau
AU - Anne Debant
AU - Frédéric Baudat
AU - Xavier Nicol
AU - Nicolas Pietrancosta
AU - Jérôme Boudeau
AU - Annie Andrieux
AU - Isabelle Arnal
AU - Adrien Antkowiak
AU - Fassier Coralie
PY - 2026
DA - 2026/10/17
PB - HAL
DO - 10.64898/2026.10.17.759799
UR - https://hal.science/hal-05843590v1
AB - Axon guidance is essential for neural circuit assembly and function. While much of the repertoire of guidance cues and receptors is known, its limited diversity cannot fully explain the remarkable complexity of the brain connectome. How temporally ordered, context-dependent intrinsic programs shape the diversity of axonal responses to guidance signals remains poorly understood. We reveal how non-canonical Wnt5a signalling repurposes the DNA repair complex RAD51/fignl1 as a downstream integrator to control retinal ganglion cell axon decision-making at the midline. We demonstrate that differential RAD51/fignl1 expression and interaction dynamics between ipsilateral and contralateral axons tunes the magnitude and temporal dynamics of F-actin nucleation, thereby encoding their trajectory choice. Our findings establish temporal control of cytoskeletal dynamics as a key determinant of axon decision-making and thereby a fundamental layer of circuit wiring. They provide a potential mechanistic framework linking mutations in the DNA repair gene RAD51 to neurodevelopmental disorders with midline guidance defects.
ER -