OBJECTIVE: In the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus. DESIGN: The authors used @entity19 in which the Hh receptor @entity20735 ( @entity20735 ) could be conditionally inactivated in a body-wide manner and @entity19 in which @entity19990 could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in @entity1 with @entity957 (SCC) by quantitative real-time PCR. RESULTS: Sonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets @entity8889 , @entity21156 and @entity2750 were increased in SCC compared with normal tissue from the same @entity1 . CONCLUSION: Here the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation.

Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the XXXX oesophagus.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity21156 :: ('64399', 'Gene') :: ['HHIP'] @entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice'] @entity957 :: ('MESH:D002294', 'Disease') :: ['oesophageal squamous cell carcinoma'] @entity19990 :: ('14632(Tax:10090)', 'Gene') :: ['Gli1'] @entity8889 :: ('2735', 'Gene') :: ['GLI1'] @entity20735 :: ('19206(Tax:10090)', 'Gene') :: ['Patched1', 'Ptch1'] @entity2750 :: ('5727', 'Gene') :: ['PTCH1']
@entity19 :: (10090,Species) :: ['murine']
