In the developing embryo, neural crest cells (NCCs) give rise to various cell types, including neural, endocrine, and craniofacial cells. Impairment of NCC development can lead to a wide spectrum of disorders known as neurocristopathies.

Three neuroscristopathies, Hirschsprung's disease (HSCR), central hypoventilation syndrome (CCHS), and neuroblastoma (NB) are some of the most common pediatric developmental disorders and frequently occur in the same patient. Despite being highly dis-similar disease states, affecting function of the bowel, control of breathing, and the development of pediatric brain cancer, all three are linked to mutations in the PHOX2B gene.

To gain a better understanding of the cellular and molecular origins of these diseases, researchers at the Riken Center for Developmental Biology in Kobe, Japan examined the effects of PHOX2B mutations in mice.

In this issue of the Journal of Clinical Investigation, Hideki Enomoto and colleagues demonstrate that a particular PHOX2B mutation disrupts the formation of neural cells, autonomic ganglia, that are required for the function of the autonomic nervous system, impairs enervation of part of the bowel, and promotes tumor development.

In a companion piece, Michael Gershon of Columbia University discusses the impact of this work on our understanding of neurocristopathies.

TITLE:Autonomic neurocristopathy-associated mutations in PHOX2B dysregulate Sox10 expression