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  • Title: Anorectal neural crest derived cell behavior after the migration of vagal neural crest derived cells is surgically disrupted: implications for the etiology of Hirschsprung's disease.
    Author: Miyahara K, Kato Y, Suzuki R, Akazawa C, Tanaka N, Koga H, Doi T, Lane GJ, Yamataka A.
    Journal: Pediatr Surg Int; 2013 Jan; 29(1):9-12. PubMed ID: 23143079.
    Abstract:
    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.
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