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

A high percentage of craniofacial malformations is ascribed to abnormalitie s in cell populations derived from the neural crest and ganglionic placodes . Both cell populations originate from the ectoderm of the head-neck area b y means of the mechanism of epitheliomesenchymal transformation (EMT). Neur al crest cells are multipotent and form the majority of the mesenchymal com partment of the head-neck area. EMT of the neural crest will stop shortly a fter closure of the neural tube. The current opinion about ganglionic placo dal cells is that they are derived from the surface ectodermal placodes aft er closure of the cranial neural tube, and transform into neurons of the se nsory ganglia only. However, additional EMT sites of the cranial neural and surface ectoderm have also been found to produce multipotent cells. Becaus e 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 surfac e ectoderm of the head-neck area during the stages of outgrowth of facial s wellings and branchial arches. The surface ectoderm was labeled by injectin g various tracker dyes into the amniotic cavity of chick embryos after clos ure of the anterior neuropore, to exclude labeling of the neural ectoderm a nd 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 c ould be shown that the entire surface ectoderm of the face and neck contrib utes cells to the underlying mesenchymal tissue, and that this phenomenon o ccurs in a higher frequency at sites of outgrowing swellings. As a conseque nce, the pathogenesis of congenital craniofacial malformations should be re considered.