R-twist gene expression during rat palatogenesis

Palatal clefting is often associated with premature fusion of cranial sutur es in human craniosynostosis syndromes, many of wh ich are characterised by mutations affecting the fibroblast growth factor receptor (FGFR) gene fami ly. In palatal fusion, epithelio-mesenchymal transition (EMT) contributes t o the dispersion of the midline epithelial seam. EMT has also been observed in neoplastic epithelial cells in relation to the acquisition of malignant characteristics where morphological changes are accompanied by rapid switc hing in the expression of fgfr2 from the epithelial type (kgfr) to the mese nchymal type (bek). The twist gene codes for a basic helix-loop-helix trans cription factor putatively involved in regulation of transcription of fgfr2 . Mutations in the TWIST gene have been described as being responsible for the Saethre-Chotzen syndrome, an autosomal dominant craniosynostosis associ ated with cleft palate as well as other disturbances of the facial skeleton . In this study we have analysed the distribution of twist transcripts duri ng rat palatogenesis in vivo from 14.5 to 17.5 days post coitum by in situ hybridisation with digoxygenin-labelled ssDNA probes. twist transcripts wer e found to be concentrated in mesenchymal cells beneath the epithelium at t he tip of the palatal shelves immediately prior to, and during fusion as we ll as in a localised epithelial area at the tip of the shelves prior to fus ion, thereby implicating twist gene expression in the process of palatogene sis. This pattern of expression illuminates the disturbances of maxillary g rowth that occur in human craniosynostotic syndromes.