Potential of extracellular matrix for non-operative treatment for Hirschsprung disease

2016 Fiscal Year Final Research Report

• Project/Area Number: 26861488
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Juntendo University
• Principal Investigator: TANAKA Nana 順天堂大学, 医学部, 准教授 (50530656)
• Research Collaborator: FUJIWARA Naho 順天堂大学, 医学部, 助教 (50530656) ; MIYAHARA Katsumi 順天堂大学, 医学部, 技術員 (00420844) ; TAKAHASHI Mirei 順天堂大学, 医学部, 研究補助員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒルシュスプルング病 / 腸管神経系 / 腸管神経堤細胞 / ラミニン / ライブイメージング / 細胞外マトリックス

Outline of Final Research Achievements

We have recently created a Venus-positive, Sox10 Tg mouse with a deletion of the endothelin-B receptor (Ednrb) gene, Sox10-Venus+/Ednrb-/- mouse, to investigate the behavior of enteric neural crest derived cells (ENCC) in HD. Firstly, we examined laminin-1 expression in the fetal gut at each developmental stage of ENCC migration. The results showed that spatiotemporal regulation of laminin-1 is required for normal ENCC migration. However, the expression of laminin-1 is altered in HD mice. Moreover, we compared the ENCC behavior when the wavefront of ENCC reaches the mid-hindgut between HD mice and control. Dissected fetal hindguts were cultured and the time-lapse images were analyzed by using Imaris software. The results showed that the track speed of ENCC advancement was markedly decreased in the HD mice compared to controls. This technique has potential for further elucidating the altered behavior of ENCC in HD.

Free Research Field

小児外科