Temporal tuning of actin nucleation by the repurposed DNA repair complex RAD51/fignl1 encodes distinct axon guidance decisions
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…
Axon guidance, crucial for forming neural circuits and their function, still has complex brain connectome wiring that remains unclear. While numerous guidance cues and receptors are identified, their limited variety cannot fully account for the intricate structure of the brain's interconnected network. The source reveals how non-canonical Wnt5a signaling modifies the DNA repair complex RAD51/fignl1 as a downstream coordinator to regulate retinal ganglion cell axon decision-making at the midline.
The study shows that the amount and timing of F-actin nucleation, which influences axon direction, are affected by the varied expression and interaction patterns of RAD51/fignl1 in ipsilateral and contralateral axons. This discovery underscores the role of temporal control of cytoskeletal dynamics in axon decision-making, representing a fundamental aspect of circuit wiring.
Moreover, the findings suggest that mutations in the DNA repair gene RAD51 could potentially contribute to neurodevelopmental disorders characterized by midline guidance issues.
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