Occurrence of DNA endoreplication in neurons.

DNA endoreplication has been repeatedly reported in protists, plants, arthropods, molluscs, fish and mammals. The same studies indicated that cells possessing endoreplicated genome are generally large-sized and highly metabolically active, suggesting that endoreplication could have a functional significance. Neurons are typically considered as fully differentiated, non-dividing cells containing a diploid genome. Despite this general rule, some papers questioned the validity of this statement and indicated that giant neurons in molluscs, supramedullary and hypothalamic magnocellular neurons in fish and Purkinje cells in vertebrate (predominantly mammalian) cerebellum present DNA contents larger than 2C. Quantitative microfluorimetric evaluation of DNA content in nerve cells of the gastropod molluscs Planorbarius corneus, Aplysia californica and Lymnaea stagnalis indicated that neuronal DNA contents range between 2C and 200.000C values. This increase in DNA content generally concerns whole-genome duplications, whereas in P. corneus endoreplication mainly applies to GC-rich sequences. The second example of endoreplicated neurons is highlighted by the large, clustered neurons located at the boundary between the medulla oblongata and spinal cord in the fish Lophius piscatorius and Diodon holacanthus. The DNA content of these neurons, evaluated by microfluorimetric methods, range from 4C in small to over 5000C in large neurons. Further experiments with AT and GC specific fluorochromes showed that the increase in DNA content is due to an amplification involving GC-rich DNAs in L. piscatorius, whereas a whole-genome endoduplication occurs in D. holacanthus. Subsequent quantitative evaluation revealed that also L. piscatorius hypothalamic magnocellular neurons, located in the preoptic and tuberal areas, largely exceed 2C. The third example is represented by nuclei of Purkinje cells isolated from the cerebellum. These results have been debated for several years, since contrasting data are present in literature. Up till now, the dilemma remains unsolved, but it is not possible to exclude that a small percentage of Purkinje neurons contain hyperdiploid and tetraploid nuclei, due to additional DNA synthesis. In order to study this topic into more detail, we here review the available data about endoreplication in invertebrate and vertebrate giant neurons and consider the possible molecular mechanisms responsible for endoreplication. Furthermore, some possible functional significances of neuron endoploidy are discussed.