Cell-cell fusion in the nervous system: Alternative mechanisms of development, injury, and repair

- The neuron theory of Ramón y Cajal states that neurons are individual cells.
- Despite the neuron theory, neurons and glia are able to fuse their plasma membranes.
- Some neurons undergo self-fusion during development and repair.
- Neurons and glia are able to form multinucleated cells.

Over a century ago, the seminal work of Ramón y Cajal revealed that the nervous system is made of individual units, the neurons, which are related to each other by contiguity rather than continuity. This view overturned the idea that the nervous system was a reticulum of fibers, a rete diffusa nervosa, as proposed and defined by Camillo Golgi. Although the neuron theory has been widely confirmed in every model system studied and constitutes the basis of modern neuroscience, evidence accumulated over the years suggests that neurons, similar to other types of cells, have the potential to fuse their membranes and undergo cell-cell fusion under certain conditions. This concept adds a substantial layer to our view of the nervous system and how it functions. Here, we bring together past and more recent discoveries on multiple aspects of neuronal fusion, discussing how this cellular event is generated, and what consequences it has for our understanding of nervous system development, disease, injury, and repair.

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