Perspectives on genetic aspects of dental patterning.

Nearly a century of speculation and experimentation has gone into trying to understand the mechanisms that establish the pattern of the differentiated heterodont dentition. Regionally differing qualitative (combinatorial) expression of regulatory genes appears to be involved in this process. Work by our laboratory and others shows that the six members of the mammalian Dlx family of homeobox genes are expressed (a) at multiple times during dental development, (b) differently at different stages, (c) in a way that is related to their genomic organization as gene-pairs linked to three of the four Hox clusters of positional patterning genes. The expression appears to be involved in jaw regionalization, tooth initiation, and tooth development. However, this expression correlates with no single aspect of dental patterning or tooth development, involves redundant and complementary function, and developmental differences between the maxillary and mandibular dentition suggest that other elements remain to be identified. For example, the possibility that quantitative aspects of gene expression specify developmental fields in the dentition has not yet been investigated. Although the maxilla and mandible develop differently, indirect evidence suggests that, especially in the future midline (incisor) regions, both jaws may be patterned by a consistent process that occurs before neural crest migration takes place, and we hypothesize that signaling factors like Sonic hedgehog and Pax transcription factors may be involved.