Axonal repair by fusion: pitfalls, consequences and solutions

In our work and as we follow the field, we have become increasingly concerned about issues in the analysis of regenerative axonal fusion. This highly efficient mechanism of regeneration occurs when a severed axon regrows, reattaches, and fuses with its own detached segment. Axonal fusion has been observed to spontaneously occur in a number of invertebrate species, and similar means of repair are now being induced in the clinic (1). Much of our knowledge regarding the molecular mechanisms that control spontaneous axonal fusion have come from studies in the nematode Caenorhabditis elegans and stemmed from the better known process of cell-cell fusion (2). However, with increasing interest in this field, we deem it important to clarify the correct methodology for the quantification of axonal fusion to prevent misleading conclusions from being drawn. Here, we define the terms associated with axonal fusion before outlining potential pitfalls associated with its incorrect analysis. Importantly, the following considerations equally apply to the similar process of regenerative dendrite fusion, which has also been characterized in C. elegans (3, 4).