INHIBITION OF MIGRATION OF NEURAL CREST-DERIVED CELLS BY THE ABNORMAL MESENCHYME OF THE PRESUMPTIVE AGANGLIONIC BOWEL OF LS/LS MICE - ANALYSIS WITH AGGREGATION AND INTERSPECIES CHIMERAS

The terminal bowel is congenitally aganglionic in Is/Is mice. The condition has been associated with an overabundance of laminin and other matrix molecules. Aggregation Is/Is ↔ C3H chimeric mice and interspecies mouse ↔ quail chimeras were constructed to test the hypothesis that the aganglionosis arises because the Is/Is gut and not the neural crest is abnormal. Demonstration of β-glucuronidase activity permitted genotypically Is/Is and C3H cells to be distinguished in the Is/Is ↔ C3H chimeras. Aganglionosis did not occur in the Is/Is ↔ C3H mice and Is/Is neurons were observed in the terminal bowel. Following backtrans-plantation of control segments of mouse gut into quail host embryos, mouse cells migrated to host targets normally colonized by cells from the neural crest; moreover, quail crest-derived cells entered the mouse gut. In contrast, cells did not migrate to these targets from presumptive aganglionic Is/Is bowel and quail crest-derived cells neither entered the Is/Is gut nor migrated through it. Laminin immunoreactivity was present in the backgrafts of murine colon and was far more abundant and widespread in those from Is/Is than in those from control animals. These data suggest that the presumptive aganglionic Is/Is bowel does not contain crest-derived cells because these cells, which are normal in Is Is mice, do not enter it. This failure of colonization may be related to the premature formation of neurons outside the abnormal gut, a response that may be promoted by the excessive secretion of laminin by the Is Is enteric mesenchyme. © 1993 Academic Press, Inc.