Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
J Clin Invest. 2012 Sep;122(9):3056-8. doi: 10.1172/JCI63884. Epub 2012 Aug 27.
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.
虽然神经嵴及其衍生物已经研究了很长时间，但对源于神经嵴的疾病（神经嵴病变）的了解并不多。在本期 JCI 中，Nagashimada 等人对神经嵴病变之一，即神经母细胞瘤（NB）与先天性巨结肠（无神经节细胞症，末端肠道）和先天性中枢性换气不足综合征（CCHS）（也称为 NB-HSCR-CCHS）的关联进行了分析，其与 PHOX2B 基因突变有关。在小鼠模型中，Nagashimada 等人证明，一种疾病相关突变可促进肿瘤发生，并破坏神经发生、交感神经节发生和神经嵴细胞对末端肠道的定植。他们还表明，突变型 PHOX2B 可导致源于神经嵴的细胞增殖减少，以及神经胶质细胞而非神经元的发育。这项工作提出了一些有趣的问题，即交感神经系统和肠神经系统可能具有共同起源，并为我们提供了新的希望，即有朝一日我们可能会了解先天性巨结肠手术后持续存在的胃肠道功能恼人异常。
