Morphogeresis of the vertebrate face

The face is one of the most intricately shaped parts of the vertebrate body. During embryogenesis the adult face develops through outgrowth of small primordia that surround the future oral and nasal cavities. Localized fusion of the maxillary, frontonasal and lateral nasal primordia then gives rise to the primary palate, separating the entrance of oral and nasal cavities. Subsequently, the secondary palate develops through outgrowth, elevation and fusion of the palatal shelves on the oral side of the maxilla. Errors in this complex series of events result in facial malformations as for example cleft palate, which is one of the most frequent birth defects in humans. We have used the mouse and the chick as model organisms to study how facial development is regulated during embryogenesis. We have characterized tissue interactions during development of the nasal region and found that the nasal placodes are essential for normal development of the nasal skeleton in the chick, and that signals from the nasal placodes regulate expression of signaling molecules in the adjacent ectoderm which may then control development of the underlying mesenchyme. The FGF family of signaling molecules has a central role in the regulation of many aspects of vertebrate embryogenesis and many processes in the adult. We show that several members of this family are expressed during early craniofacial development and we have analyzed facial morphogenesis in mouse embryos deficient in Fgf8 in the facial area. These mutants develop severe facial defects including a midfacial cleft, and defect in the olfactory epithelium demonstrating that FGF signaling is of key importance for facial development. Using a candidate approach, we have identified Pax3, Tbx2, Erm and Pea3 as FGF regulated genes in the facial mesenchyme. We have then performed a systematic screen for FGF inducible genes. Among the genes identified in this screen are genes that have not previously been implicated with functions downstream of Fgf signaling and novel genes that have not been studied at all. Characterization of the function of these genes will be a major focus of our research in the next years.