Evolutionary modification of development in mammalian teeth: Quantifying gene expression patterns and topography

Abstract

The study of mammalian evolution often relies on detailed analysis of dental morphology. For molecular patterning to play a role in dental evolution, gene expression differences should be linkable to corresponding morphological differences. Because teeth, like many other structures, are complex and evolution of new shapes usually involves subtle changes, we have developed topographic methods by using Geographic Information Systems. We investigated how genetic markers for epithelial signaling centers known as enamel knots are associated with evolutionary divergence of molar teeth in two rodent species, mouse and vole. Our analysis of expression patterns of Fgf4, Lef1, p21, and Shh genes in relation to digital elevation models of developing tooth shapes shows that molecular prepatterns predict the lateral cusp topography more than a day in advance. A heterotopic shift in the molecular prepatterns can be implicated in the evolution of mouse molar, changing locations from which historically homologous cusps form. The subtle but measurable heterotopic shifts may play a large role in the evolution of tooth cusp topographies. However, evolutionary increase in the number of longitudinal cusps in vole molar has involved accelerated longitudinal growth and iterative addition of new cusps without changes in lateral cusp topography. The iterative addition of cusps after the establishment of lateral cusp topography may limit the independence of individual morphological features used in evolutionary studies. The diversity of mammalian molar patterns may largely result from the heterotopic and iterative processes.

Integrating the genotype and phenotype in hominid paleontology

“…Other examples of population-based approaches and comparative cross-taxon gene expression studies are proving to be successful in the search for the genetic mechanisms underlying other types of phenotypic evolution (5,8,9,123,124). For example, when Jernvall and colleagues (9, 124) studied gene expression patterns in mouse and vole molar development, they found four genes that have spatial expression patterns that correlate with the morphological differences between these two rodents.…”

“…This is most evident in studies of large-scale organismal evolution, such as the origins of animal body plans during the Cambrian period (1-3), the evolution of limbs (4)(5)(6), and the appearance of teeth in early fishes (7). Even within more restricted groups, such as mammals, new knowledge of dental developmental genetics has elucidated evolutionary phenomenon (8)(9)(10).…”

Signaling Networks Regulating Tooth Organogenesis and Regeneration, and the Specification of Dental Mesenchymal and Epithelial Cell Lineages

“…In addition to directing crown formation, in molars it determines the positions of the secondary enamel knots which in turn mark the positions of the cusp tips in the molar crown ( Fig. 2B) (Jernvall et al 2000). Wnts are important upstream regulators of enamel knots as shown by the requirement of Lef1 for Fgf4 expression in the enamel knot (Kratochwil et al 2002) and the induction of new enamel knots and placodes by forced activation of Wnt/b-catenin signaling in oral epithelium (Järvinen et al 2006;Wang et al 2009).…”

A gene network model accounting for development and evolution of mammalian teeth

“…Of those, 12 are signaling molecules belonging to the Bmp, Fgf, Shh, and Wnt gene families. They are expressed in nested patterns around the knots and their expression domains predict future cusp patterns (11). Established candidate molecules for activators include bone morphogenetic proteins (BMPs), which induce differentiation markers in the dental epithelia, associated with the cessation of mitosis in the knot (12,13).…”