POLARIZING ACTIVITY, SONIC HEDGEHOG, AND TOOTH DEVELOPMENT IN EMBRYONIC AND POSTNATAL MOUSE

Tooth development involves reciprocal epithelial-mesenchymal interacti ons, polarized growth, mesenchyme condensation, and complex morphogene tic events. Because these processes bear similarities to those occurri ng in the developing limb, we asked whether morphogenetic signals foun d in the limb also occur in the developing tooth, We grafted mouse emb ryo tooth germs to the anterior margin of host chick embryo wing buds and determined whether the dental tissues had polarizing activity. Ind eed, the grafts induced supernumerary digits, Activity of both molar a nd incisor tooth germs increased from bud to cap stages and was maxima l at late bell stage in newborn, With further development the polarizi ng activity began to decrease, became undetectable in adult molar mese nchyme but persisted in incisor mesenchyme, correlating with the fact that incisors grow throughout postnatal life while molars do not, When different portions of neonatal incisors were assayed, a clear proximo -distal gradient of activity was apparent, with maximal activity restr icted to the most proximal portion where undifferentiated mesenchyme a nd enamel organ reside. In situ hybridizations demonstrated that prior to induction of supernumerary digits, the tooth germ grafts induced e xpression in host tissue of Hoxd-12 and Hoxd-13, In addition, whole-mo unt in situ hybridizations and immunohistochemistry showed that develo ping tooth germs express Sonic hedgehog (Shh). Shh expression was firs t detected in bud stage tooth germs; at later stages Shh transcripts w ere prominent in enamel knot and differentiating ameloblasts at the cu spal region, We concluded that tooth germs possess polarizing activity and produce polarizing factors such as Shh, As in the limb, these fac tor(s) and activity probably play key roles in establishing polarity a nd regulating morphogenesis during early tooth development. Given its subsequent association with differentiating ameloblasts, Shh probably participates also in cytogenetic events during odontogenesis. (C) 1996 Wiley-Liss, Inc.