MYCN in Neural Crest Development

As described in Chap. 4, MYCN amplification contributes to the clinically aggressive behavior of NB tumors (Seeger et al. 1985). MYCN has also been shown to play an important role in the development of sympathetic neurons. Deletion of the MYCN gene in animal models leads to a reduction in the number of mature neurons in the dorsal root and sympathetic ganglia (Sawai et al. 1993; Stanton et al. 1992). In addition, MYCN can stimulate post-mitotic sympathetic neurons to re-enter the cell cycle and enhance their survival (Wartiovaara et al. 2002). In avian embryos, migrating neural crest cells express MYCN. After cessation of the major wave of neural crest cell migration, MYCN expression is heterogeneous in the dorsal root and sympathetic ganglia, being more highly expressed in the nucleus of neuronal cells and decreased in Schwann and glial cells. In explants of neural crest cells in vitro, expression of MYCN stimulates an increase in differentiated neural crest cells without affecting proliferation. Implantation of MYCN-transduced neural crest cells in vivo leads to a massive migration of cells into the sympathetic ganglia and an increase in differentiated cells; thus, MYCN functions at an early phase of neural crest development increasing their migratory potential and a later phase promoting their neural differentiation (Wakamatsu et al. 1997).

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