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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

NPARM in PHOX2B: why some things just should not be expanded.

Although the neural crest and its derivatives have been studied for a very long time, disorders of derivatives of the crest, the neurocristopathies, are not well understood. In this issue of the JCI, Nagashimada et al. provide an elegant analysis of one neurocristopathy, the association of neuroblastoma (NB) with Hirschsprung disease (HSCR) (aganglionosis of the terminal bowel) and congenital central hypoventilation syndrome (CCHS) (also known as NB-HSCR-CCHS), linked to mutations in PHOX2B. In a mouse model, Nagashimada et al. demonstrate that a disease-linked mutation promotes tumorigenesis and disrupts neurogenesis, sympathetic gangliogenesis, and crest cell colonization of the terminal bowel. They also show that mutant PHOX2B results in decreased proliferation of crest-derived cells and the development of glia at the expense of neurons. The work raises intriguing issues about the possible common origin of sympathetic and enteric nervous systems and provides new hope that we may someday understand the vexing abnormalities in gastrointestinal function that persist after the surgical treatment of HSCR.[1]

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