Background/purpose: In Hirschsprung's disease (HD), thick extrinsic nerve fibers can be associated with the aganglionic segment in the anorectum. We surgically disrupted the migration of vagal neural crest cell-derived cells (vagal NCC) in embryos from transgenic mice we created previously (SOX10-VENUS Tg) which have the SOX10 gene labeled with Venus (V), a green fluorescent protein, to observe sacral NCC activity in the anorectum.
Method: Proximal colon harvested from SOX10-VENUS Tg embryos on day 10.5 (n = 10) was transected at the ascending colon. V-positive sacral NCC in the anorectum were observed during organ culture under fluorescence stereoscopic microscopy, and compared with non-transected control specimens (n = 10).
Results: In transected specimens, no V-positive sacral NCC were identified initially in the anorectum. By day 2, there were thick beaded sacral NCC in the anorectum in 6/10 (60 %) that migrated steadily to the transected end over 3-4 days. In controls, thinner and shorter V-positive sacral NCC began migrating cranially on day 2, and were met by distally migrating vagal NCC.
Conclusion: Disruption of vagal NCC migration appears to induce sacral NCC activity in the anorectum, suggesting that thick extrinsic nerve fibers seen in HD may be a secondary phenomenon.