How do genes make teeth to order through development?

This introduction to new patterning theories for the vertebrate dentition outlines the historical concepts to explain graded sequences in tooth shape in mammals (incisors, canines, premolars, molars) which change in evolution in a linked manner, constant for each region. The classic developmental models for shape regulation, known as the 'regional field' and 'dental clone' models, were inspired by the human dentition, where it is known that the last tooth in each series is the one commonly absent. The mouse, as a valuable experimental model, has provided data to test these models and more recently, based on spatial-temporal gene expression data, the 'dental homeobox code' was proposed to specify regions and regulate tooth shape. We have attempted to combine these hypotheses in a new model of the combinatorial homeobox gene expression pattern with the clone and field theories in one of 'co-operative genetic interaction'. This also explains the genetic absence of teeth in humans ascribed to point mutations in mesenchymally expressed genes, which affect tooth number in each series.