Patched1 is essential for nasal pit invagination in mouse

Abstract

Hedgehog (Hh) signalling plays a critical role in vertebrate face formation. To understand the role of the receptor Patched1 (PTCH1) in facial development, we are using the Wnt1–Cre to conditionally inactivate Ptch1 in neural crest cells. This results in constitutive, ligand-independent upregulation of the Hh pathway in the majority of mesenchymal cells in the face. We have shown for the first time that Ptch1 deletion drastically alters the shape of the nasal pit and disrupts its ability to invaginate. While neural crest cells are able to migrate and populate the developing nasal processes, they appear to form part of a loosely organised mesenchyme, unable to respond to FGF signals from the overlying epithelium and consequently fail to specify the lateral nasal process. We find that the structure of the overlying nasal pit epithelium is perturbed, evidenced by changes in cell–cell contacts and actin organisation. In summary, our analysis of Ptch1 conditional mutants has revealed unexpected changes in the shape and structure of cells of the nasal pit epithelium, which may explain why invagination is perturbed. These findings identify novel roles mediated by PTCH1 that are essential for correct morphogenesis of the nasal pit. Furthermore, they indicate that strict, spatio-temporal control of Hh signalling helps to define face shape in the embryo.