Modeling Development and Disease in Our "Second" Brain

The enteric nervous system (ENS) in our gastrointestinal tract, nicknamed the “second brain”, is responsible for normal gut function and peristaltic contraction. Embryonic development of the ENS involves the colonization of the gut wall from one end to the other by a population of proliferating neural crest (NC) cells. Failure of these cells to invade the whole gut results in the relatively common, potentially fatal condition known as Hirschsprung disease (HSCR). Cellular automata models provide insight into the colonization process at both the individual cell-level and population-level. Our models generated experimentally testable predictions, which have subsequently been confirmed. The model results imply that HSCR is chiefly a NC cell proliferation defect and not, as previously thought, a NC cell motility defect. These results have important implications for HSCR; namely stochastic effects can determine success or failure of the colonization process for a certain range of NC cell proliferation rates.