Teeth have been missing from birds (Aves) for at least 60 million years. Ho
wever, in the chick oral cavity a rudiment forms that resembles the lamina
stage of the mammalian molar tooth germ. We have addressed the molecular ba
sis for this secondary loss of tooth formation in Aves by analyzing in chic
k embryos the status of molecular pathways known to regulate mouse tooth de
velopment. Similar to the mouse dental lamina, expression of Fgf8, Pitx2, B
arx1, and Pax9 defines a potential chick odontogenic region. However, the e
xpression of three molecules involved in tooth initiation, Bmp4, Msx1, and
Msx2, are absent from the presumptive chick dental lamina. In chick mandibl
es, exogenous bone morphogenetic protein (BMP) induces Msx expression and t
ogether with fibroblast growth factor promotes the development of Sonic hed
gehog expressing epithelial structures. Distinct epithelial appendages also
were induced when chick mandibular epithelium was recombined with a tissue
source of BMPs and fibroblast growth factors, chick skin mesenchyme. These
results show that, although latent, the early signaling pathways involved
in odontogenesis remain inducible in Aves and suggest that loss of odontoge
nic Bmp4 expression may be responsible for the early arrest of tooth develo
pment in living birds.