Nearly a century of speculation and experimentation has gone into tryi
ng to understand the mechanisms that establish the pattern of the diff
erentiated heterodont dentition. Regionally differing qualitative (com
binatorial) expression of regulatory genes appears to be involved in t
his process. Work by our laboratory and others shows that the six memb
ers of the mammalian Dlx family of homeobox genes are expressed (a) at
multiple times during dental development, (b) differently at differen
t stages, (c) in a way that is related to their genomic organization a
s gene-pairs linked to three of the four Hox clusters of positional pa
tterning genes. The expression appears to be involved in jaw regionali
zation, tooth initiation, and tooth development. However, this express
ion correlates with no single aspect of dental patterning or tooth dev
elopment, involves redundant and complementary function, and developme
ntal differences between the maxillary and mandibular dentition sugges
t that other elements remain to be identified. For example, the possib
ility that quantitative aspects of gene expression specify development
al 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 ma
y 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.