title: On the difficulty of increasing dental complexity.
abstract: One of the fascinating aspects of the history of life is the apparent increase in morphological complexity through time, a well known example being mammalian cheek tooth evolution. In contrast, experimental studies of development more readily show a decrease in complexity, again well exemplified by mammalian teeth, in which tooth crown features called cusps are frequently lost in mutant and transgenic mice. Here we report that mouse tooth complexity can be increased substantially by adjusting multiple signalling pathways simultaneously. We cultured teeth in vitro and adjusted ectodysplasin (EDA), activin A and sonic hedgehog (SHH) pathways, all of which are individually required for normal tooth development. We quantified tooth complexity using the number of cusps and a topographic measure of surface complexity. The results show that whereas activation of EDA and activin A signalling, and inhibition of SHH signalling, individually cause subtle to moderate increases in complexity, cusp number is doubled when all three pathways are adjusted in unison. Furthermore, the increase in cusp number does not result from an increase in tooth size, but from an altered primary patterning phase of development. The combination of a lack of complex mutants, the paucity of natural variants with complex phenotypes, and our results of greatly increased dental complexity using multiple pathways, suggests that an increase may be inherently different from a decrease in phenotypic complexity.
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
authors.forename: Enni
authors.initials: E
authors.lastname: Harjunmaa
authors.forename: Aki
authors.initials: A
authors.lastname: Kallonen
authors.forename: Maria
authors.initials: M
authors.lastname: Voutilainen
authors.forename: Keijo
authors.initials: K
authors.lastname: Hämäläinen
authors.forename: Marja L
authors.initials: ML
authors.lastname: Mikkola
authors.forename: Jukka
authors.initials: J
authors.lastname: Jernvall
mesh_terms: D028341:Activins / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D005075:Biological Evolution; D015509:Developmental Biology; D053331:Ectodysplasins / Q000378:metabolism / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008963:Molar / Q000033:anatomy & histology* / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D009154:Mutation; D009924:Organ Culture Techniques; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053331:Ectodysplasins; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; C422405:activin A; D028341:Activins