Subcellular second messenger networks drive distinct repellent-induced axon behaviors

Sarah Baudet, Yvrick Zagar, Fiona Roche, Claudia Gomez-Bravo, Sandrine Couvet, Johann Bécret, Morgane Belle, Juliette Vougny, Sinthuya Uthayasuthan, Oriol Ros and Xavier Nicol ()
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Sarah Baudet: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Yvrick Zagar: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Fiona Roche: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Claudia Gomez-Bravo: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Sandrine Couvet: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Johann Bécret: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Morgane Belle: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Juliette Vougny: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Sinthuya Uthayasuthan: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Oriol Ros: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Xavier Nicol: Sorbonne Université, INSERM, CNRS, Institut de la Vision

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Second messengers, including cAMP, cGMP and Ca2+ are often placed in an integrating position to combine the extracellular cues that orient growing axons in the developing brain. This view suggests that axon repellents share the same set of cellular messenger signals and that axon attractants evoke opposite cAMP, cGMP and Ca2+ changes. Investigating the confinement of these second messengers in cellular nanodomains, we instead demonstrate that two repellent cues, ephrin-A5 and Slit1, induce spatially segregated signals. These guidance molecules activate subcellular-specific second messenger crosstalk, each signaling network controlling distinct axonal morphology changes in vitro and pathfinding decisions in vivo.

Date: 2023
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DOI: 10.1038/s41467-023-39516-z

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