It has been known since the 1950s that the enteric nervous system is formed from cells that arise from the neural crest.1 The enteric neurones mainly arise from the vagal neural crest of the developing hind brain and colonise the gut in a rostro caudal migration but some seem to arrive in the hind gut from the lumbosacral level via a caudo rostral wave of colonisation. The neural crest cells that migrate and colonise the gut are committed to become neuroblasts or neuronal support cells, glioblasts; however, differentiation into neurones and glial cells seems not to take place until they have reached their final resting places in the gut. Movement through the gut mesenchyme, survival in the gut and differentiation into mature cells is strongly influenced by contacts with the microenvironment which consists of other cells in the mesenchyme, neural crest, and the extracellular matrix. The extracellular matrix components provide directional clues to migrating neural crest cells and together with neighbouring cells provide some of the signals for crest cell differentiation. For example, the appearance of neural crest cells in the gut is preceded by expression of extracellular matrix molecules2 and other factors such as glial derived neurotropic factor (GDNF) ensure survival of committed neuroblasts.3 Thus defects of the neural crest cells themselves or alteration of the microenvironment …