The role of effectors of the activin signalling pathway, activin receptorsIIA and IIB, and Smad2, in patterning of tooth development

The gene for activin betaA is expressed in the early odontogenic mesenchyme of all murine teeth but mutant mice show a patterning defect where incisor s and mandibular molars fail to develop but maxillary molars develop normal ly. In order to understand why maxillary molar tooth development can procee d in the absence of activin, we have explored the role of mediators of acti vin signalling in tooth development. Analysis of tooth development in activ in receptor II and Smad2 mutants shows that a similar tooth phenotype to ac tivin betaA mutants can be observed. In addition, we identify a novel downs tream target of activin signalling, the Iroquois-related homeobox gene, Irx 1, and show that its expression in activin betaA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly sug gest that other transforming growth factor beta molecules are not stimulati ng the activin signalling pathway in the absence of activin. This was confi rmed by a non-genetic approach using exogenous soluble receptors to inhibit all activin signalling in tooth development, which reproduced the genetic phenotypes. Activin, thus, has an essential role in early development of in cisor and mandibular molar teeth but this pathway is not required for devel opment of maxillary molars.