N-cadherin and β1-integrins cooperate during the development of the enteric nervous system

Abstract : Cell adhesion controls various embryonic morphogenetic processes, including the development of the enteric nervous system (ENS). Ablation of β1-integrin (β1-/-) expression in enteric neural crest cells (ENCC) in mice leads to major alterations in the ENS structure caused by reduced migration and increased aggregation properties of ENCC during gut colonization, which gives rise to a Hirschsprung's disease-like phenotype. In the present study, we examined the role of N-cadherin in ENS development and the interplay with β1 integrins during this process. The Ht-PA-Cre mouse model was used to target gene disruption of N-cadherin and β1 integrin in migratory NCC and to produce single- and double-conditional mutants for these two types of adhesion receptors. Double mutation of N-cadherin and β1 integrin led to embryonic lethality with severe defects in ENS development. N-cadherin-null (Ncad-/-) ENCC exhibited a delayed colonization in the developing gut at E12.5, although this was to a lesser extent than in β1-/- mutants. This delay of Ncad-/- ENCC migration was recovered at later stages of development. The double Ncad-/-; β1-/- mutant ENCC failed to colonize the distal part of the gut and there was more severe aganglionosis in the proximal hindgut than in the single mutants for N-cadherin or β1-integrin. This was due to an altered speed of locomotion and directionality in the gut wall. The abnormal aggregation defect of ENCC and the disorganized ganglia network in the β1-/- mutant was not observed in the double mutant. This indicates that N-cadherin enhances the effect of the β1-integrin mutation and demonstrates cooperation between these two adhesion receptors during ENS ontogenesis. In conclusion, our data reveal that N-cadherin is not essential for ENS development but it does modulate the modes of ENCC migration and acts in concert with β1-integrin to control the proper development of the ENS.
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Contributor : Perrine Paul-Gilloteaux <>
Submitted on : Monday, February 19, 2018 - 12:00:30 PM
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Florence Broders-Bondon, Perrine Paul-Gilloteaux, Camille Carlier, Glenn Radice, Sylvie Dufour. N-cadherin and β1-integrins cooperate during the development of the enteric nervous system. Developmental Biology, Elsevier, 2012, 364 (2), pp.178 - 191. ⟨10.1016/j.ydbio.2012.02.001⟩. ⟨hal-01712255⟩



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