beta 1 integrins are required for the invasion of the caecum and proximal hindgut by enteric neural crest cells

Abstract

Integrins are the major adhesive receptors for extracellular matrix and have various roles in development. To determine their role in cell migration, the gene encoding the beta 1 integrin subunit (Itgb1) was conditionally deleted in mouse neural crest cells just after their emigration from the neural tube. We previously identified a major defect in gut colonisation by conditional Itgb1-null enteric neural crest cells (ENCCs) resulting from their impaired migratory abilities and enhanced aggregation properties. Here, we show that the migration defect occurs primarily during the invasion of the caecum, when Itgb1-null ENCCs stop their normal progression before invading the caecum and proximal hindgut by becoming abnormally aggregated. We found that the caecum and proximal hindgut express high levels of fibronectin and tenascin-C, two well-known ligands of integrins. In vitro, tenascin-C and fibronectin have opposite effects on ENCCs, with tenascin-C decreasing migration and adhesion and fibronectin strongly promoting them. Itgb1-null ENCCs exhibited an enhanced response to the inhibitory effect of tenascin-C, whereas they were insensitive to the stimulatory effect of fibronectin. These findings suggest that beta 1 integrins are required to overcome the tenascin-C-mediated inhibition of migration within the caecum and proximal hindgut and to enhance fibronectin-dependent migration in these regions.