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

Abstract

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.

Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion inCaenorhabditis elegans

“…The regenerative ability of axons following injury has been previously described in vertebrates and invertebrates (Cajal 1899; Hoy et al 1967; Devor 1976; Bradbury et al 2002; Fernandez-Gonzalez et al 2002; Giordano-Santini et al 2016). The morphological and molecular changes that occur following dendritic severing remain mostly unexplored (Standler and Bernstein 1982; Oren-Suissa and Podbilewicz 2010; Oren-Suissa et al 2010; Stone et al 2010, 2014; Nawabi et al 2012; Song et al 2012; Rao et al 2016; Tao et al 2016).…”

“…Axonal fusion after injury is crucial for reestablishing synaptic contacts, to prevent degeneration, and for regaining neurological functionality (Hilliard 2009; Giordano-Santini et al 2016). Although eff-1 mutants failed to fuse broken axons (Ghosh-Roy et al 2010), eff-1 mutants succeed to merge injured dendrites.…”

“…The nematode Caenorhabditis elegans is a powerful model to study neuronal regeneration after injury (Chisholm et al 2016; Giordano-Santini et al 2016). It has been recently found that injured axons of motor and mechanosensory neurons regrow and, in some cases, fuse after in vivo severing using laser surgery (Yanik et al 2004; Bourgeois and Ben-Yakar 2007; Ghosh-Roy and Chisholm 2010; Ghosh-Roy et al 2010; Neumann et al 2011; Giordano-Santini et al 2016).…”

“…It has been recently found that injured axons of motor and mechanosensory neurons regrow and, in some cases, fuse after in vivo severing using laser surgery (Yanik et al 2004; Bourgeois and Ben-Yakar 2007; Ghosh-Roy and Chisholm 2010; Ghosh-Roy et al 2010; Neumann et al 2011; Giordano-Santini et al 2016). Moreover, screens for genes with roles in axon regrowth have identified many genes required for axon regeneration (Gabel et al 2008; Ghosh-Roy and Chisholm 2010; Nix et al 2014; Chisholm et al 2016).…”

Sub-acute Sclerosing Pan-encephalitis in a 5 Years Old Child: A Response to Intravenous Immunoglobulin and Steroids

“…Cell to cell spread of RNP complex in the brain using cell-cell fusion events takes place over few years before clinical onset. [4,5] During the slow replication of the RNA, naturally occurring mutation happens at constant rate and allowed to build up in numbers due to the absence of lytic infection that otherwise select the more functionally fit wild strain. Furthermore, there is evident of presence of hypermutation attributed to cellular RNA dependent adenosine deaminase enzyme.…”