Remodeling of the periodic actin-spectrin scaffold supports axonal development and branching

The morphology of neurons is critical for circuit formation in the nervous system, with neuronal arborization requiring precise cytoskeletal and membrane remodeling. The axonal membrane-associated skeleton (MPS) is a scaffold made of actin and spectrin that plays a key role in maintaining axonal integrity. While some of its functions have been characterized, its dynamics during axonal branching remain unknown. The established role of actin, microtubules and mitochondria in regulating branching motivate us to investigate their interplay with the MPS in the context of branch initiation. We hypothesize that branching along immature axons occurs in segments devoid of MPS, and that branch initiation along mature axons requires MPS disruption. Using super-resolution microscopy, live-cell imaging, endogenously-tagged probes and optogenetic perturbations, we will track MPS dynamics, induce branching, and manipulate scaffolds to understand this phenomenon. This will provide insights into how MPS dynamics coordinate axonal plasticity, with implications for neurodevelopmental and neurodegenerative disorders.