PhD Scientific Days 2020

Theoretical and Translational I. Posters

Essential Role of the Avian Ceca for Formation of the Hindgut Enteric Nervous System

Előadó neve

Kovács, Tamás, MSc

Előadó munkahelye

Semmelweis University, Department of Anatomy, Histology and Embryology

Előadó telefonszáma

06702285757

Előadó e-mail címe

kovacs.tamas@med.semmelweis-univ.hu

Az előadás címe

Essential Role of the Avian Ceca for Formation of the Hindgut Enteric Nervous System

Szerző(k) neve és munkahelye

Tamas Kovacs1, Nandor Nagy1, Ryo Hotta2, Allan M. Goldstein2
1 Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
2 Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Szekció

Theoretical and Translational I. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Neurosciences

Összefoglaló szövege

The enteric nervous system (ENS), which is derived from neural crest cells (NCC) during gut development, represents the neuronal innervation of the gastrointestinal tract and is critical for regulating normal intestinal function. Compromised NCC migration can lead to Hirschsprung Disease, which is characterized by an aganglionic distal bowel. We find that removal of the ceca, a paired structure present at the midgut-hindgut junction in avian intestine, leads to incomplete NCC colonization of the hindgut, suggesting that the ceca are required for ENS development. To test this, we replaced the ceca of embryonic day 6 (E6) wild-type chicks with ceca from transgenic GFP chicks. Interestingly, the entire hindgut ENS arises from the GFP+ ceca-derived NCC population. Comparative transcriptome profiling of the cecal buds compared to the inter-ceca gut shows that the non-canonical Wnt signaling pathway is preferentially expressed in the cecal buds. Specifically, Wnt11, a non-canonical Wnt protein, is highly expressed in the ceca, as confirmed by RNA in situ hybridization, leading us to hypothesize that cecal expression of Wnt11 is important for normal NCC colonization of the hindgut. We used avian intestinal organ cultures at E5, when NCC have not yet reached the ceca, and at E6, when NCC are entering the proximal hindgut, to test this hypothesis. Cultures were treated with soluble antagonists of the canonical (XAV939) and non-canonical (Y-27632) Wnt pathways. Treatment with XAV939 had no effect, while Y-27632 arrested NCC migration in E5 explants and led to hindgut aganglionosis. While removal of the ceca leads to failure of NCC colonization of the hindgut, placement of Wnt11 protein-coated beads at the base of the resected ceca rescues this phenotype. These results confirm an important role for Wnt11 signaling in the ceca in promoting normal migration of enteric NCC and complete formation of the hindgut ENS.

Additional Information

Supervisor: Nándor Nagy
E-mail address: nagy.nandor@med.semmelweis-univ.hu

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4612

Start

11:20

End

11:23

Authors (legacy)

Tamas Kovacs1, Nandor Nagy1, Ryo Hotta2, Allan M. Goldstein2
1 Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
2 Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA