Somatic Tetraploidy in Vertebrate Neurons: Implications in Physiology and Pathology

The presence of polyploid neurons in the vertebrate nervous system has been a subject of debate since the 1960s. At that time, Purkinje cells were proposed to be tetraploid, but technical limitations impeded to reach a clear conclusion, and the current belief is that most vertebrate neurons are diploid. By using up-to-date approaches we have recently demonstrated the existence of a subpopulation of tetraploid retinal ganglion cells (RGCs) in the vertebrate retina. In the chick, these neurons show large somas and extensive dendritic trees and most of them express a marker specific for RGCs innervating a specific lamina of the optic tectum. We have also demonstrated that these neurons are generated in response to nerve growth factor (NGF) acting through the neurotrophin receptor p75 (p75(NTR)), which induces E2F1 activity and cell cycle re-entry in migrating RGC neuroblasts lacking retinoblastoma (Rb) protein. We have also showed that brain-derived neurotrophic factor (BDNF) prevents G(2)/M transition in the tetraploid RGCs, thus being crucial for the maintenance of the tetraploid status as well as the survival of these neurons. The realization that tetraploid neurons can be readily observed in the vertebrate nervous system has important physiological consequences, which are discussed in this commentary.