Migration Defects

As the gut develops, neural crest stem cells migrate from the esophagus to form ganglia that will innervate the hindgut. In Hirschsprung disease, these enteric ganglia are missing. Iwashita et al. tested whether this disease could be caused by defects in the ability of the neural crest cells to migrate to the hindgut. Gene-expression profiling of the RNA content of isolated gut neural crest stem cells revealed elevated expression of genes known to be defective in Hirschsprung disease patients. One of these, Ret, is a receptor for glial-derived neurotrophic factor (GDNF) and, like GDNF itself, is necessary for stem cell migration. Thus, Ret deficiency causes Hirschsprung disease by impairing the migration of neural crest stem cells into the distal gut. T. Iwashita, G. M. Kruger, R. Pardal, M. J. Kiel, S. J. Morrison, Hirschsprung disease is linked to defects in neural crest stem cell function. Science 301, 972-976 (2003). [Abstract] [Full Text]