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 ls/ls mice. The condition has been associated with an overabundance of laminin and other matrix molecules. Aggregation ls/ls<==>C3H chimeric mice and interspecies mouse<==>quail chimeras were constructed to test the hypothesis that the aganglionosis arises because the ls/ls gut and not the neural crest is abnormal. Demonstration of beta-glucuronidase activity permitted genotypically ls/ls and C3H cells to be distinguished in the ls/ls<==>C3H chimeras. Aganglionosis did not occur in the ls/ls<==>C3H mice and ls/ls neurons were observed in the terminal bowel. Following bactransplantation 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 ls/ls bowel and quail crest-derived cells neither entered the ls/ls 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 ls/ls than in those from control animals. These data suggest that the presumptive aganglionic ls/ls bowel does not contain crest-derived cells because these cells, which are normal in ls/ls 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 ls/ls enteric mesenchyme.
Rothman
T P
TP
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Goldowitz
D
D
Gershon
M D
MD
D000818:Animals; D002465:Cell Movement; D002678:Chimera; D003370:Coturnix; D005260:Female; D005724:Ganglia / Q000002:abnormalities*; D007422:Intestines / Q000196:embryology* / Q000294:innervation* / Q000637:transplantation; D007797:Laminin / Q000032:analysis; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009432:Neural Crest / Q000166:cytology*; D011247:Pregnancy
D007797:Laminin