Noggin is required for early development of murine upper incisors.

BMP signaling plays crucial roles in the development of many organs, including the tooth. Equally important is BMP signaling homeostasis, as demonstrated by multiple organ defects in mice lacking the extracellular BMP antagonist Noggin. Here, we show that Noggin is initially expressed in the maxillary mesenchyme adjunct to the upper incisor at the initiation stage, and then in the developing teeth, including incisors and molars, from the bud stage. Noggin mutants develop normal molars and mandibular incisors, but form a single, medially located upper incisor that is arrested at the late bud stage. Histological and molecular marker analyses demonstrated that two distinct upper incisor placodes initiate independently at E11.5, but begin to fuse at E12.5, coupling with elevated cell proliferation rates in the developing tooth germs. We further found that Chordin and Gremlin, two other BMP antagonists, are co-expressed with Noggin in the developing lower incisor and molar teeth. These observations indicate the importance of BMP signaling homeostasis, and suggest a functional redundancy between BMP antagonists during tooth development.