Epithelio-mesenchymal transformation in the embryonic face: implications for craniofacial malformations

A high percentage of craniofacial malformations is ascribed to abnormalities in cell populations derived from the neural crest and ganglionic placodes. Both cell populations originate from the ectoderm of the head-neck area by means of the mechanism of epithelio-mesenchymal transformation (EMT). Neural crest cells are multipotent and form the majority of the mesenchymal compartment of the head-neck area. EMT of the neural crest will stop shortly after closure of the neural tube. The current opinion about ganglionic placodal cells is that they are derived from the surface ectodermal placodes after closure of the cranial neural tube, and transform into neurons of the sensory ganglia only. However, additional EMT sites of the cranial neural and surface ectoderm have also been found to produce multipotent cells. Because of the fact that most craniofacial malformations develop after closure of the cranial neural tube, in this study we focused on the EMT of the surface ectoderm of the head-neck area during the stages of outgrowth of facial swellings and branchial arches. The surface ectoderm was labeled by injecting various tracker dyes into the amniotic cavity of chick embryos after closure of the anterior neuropore, to exclude labeling of the neural ectoderm and the neural crest. After various incubation periods, ranging from 0–24 h, labeled cells were found in the mesenchymal compartment scattered over the embryonic face and neck, originating from non-placodal as well as placodal surface ectoderm. Thus, besides the neural ectoderm and neural crest, it could be shown that the entire surface ectoderm of the face and neck contributes cells to the underlying mesenchymal tissue, and that this phenomenon occurs in a higher frequency at sites of outgrowing swellings. As a consequence, the pathogenesis of congenital craniofacial malformations should be reconsidered. Received: 15 November 1999 / Accepted: 27 January 2000