title: A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition.
abstract: Changes in tooth shape have played a major role in vertebrate evolution with modification of dentition allowing an organism to adapt to new feeding strategies. The current view is that molar teeth evolved from simple conical teeth, similar to canines, by progressive addition of extra "cones" to form progressively complex multicuspid crowns. Mammalian incisors, however, are neither conical nor multicuspid, and their evolution is unclear. We show that hypomorphic mutation of a cell surface receptor, Lrp4, which modulates multiple signaling pathways, produces incisors with grooved enamel surfaces that exhibit the same molecular characteristics as the tips of molar cusps. Mice with a null mutation of Lrp4 develop extra cusps on molars and have incisors that exhibit clear molar-like cusp and root morphologies. Molecular analysis identifies misregulation of Shh and Bmp signaling in the mutant incisors and suggests an uncoupling of the processes of tooth shape determination and morphogenesis. Incisors thus possess a developmentally suppressed, cuspid crown-like morphogenesis program similar to that in molars that is revealed by loss of Lrp4 activity. Several mammalian species naturally possess multicuspid incisors, suggesting that mammals have the capacity to form multicuspid teeth regardless of location in the oral jaw. Localized loss of enamel may thus have been an intermediary step in the evolution of cusps, both of which use Lrp4-mediated signaling.
authors.affiliation: Department of Craniofacial Development, Dental Institute, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohazama
authors.forename: James
authors.initials: J
authors.lastname: Blackburn
authors.forename: Thantrira
authors.initials: T
authors.lastname: Porntaveetus
authors.forename: Masato S
authors.initials: MS
authors.lastname: Ota
authors.forename: Hong Y
authors.initials: HY
authors.lastname: Choi
authors.forename: Eric B
authors.initials: EB
authors.lastname: Johnson
authors.forename: Philip
authors.initials: P
authors.lastname: Myers
authors.forename: Shelly
authors.initials: S
authors.lastname: Oommen
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Eto
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Fraser
authors.forename: J Todd
authors.initials: JT
authors.lastname: Streelman
authors.forename: Ulyses F J
authors.initials: UF
authors.lastname: Pardiñas
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Tucker
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Ortiz
authors.forename: Cyril
authors.initials: C
authors.lastname: Charles
authors.forename: Laurent
authors.initials: L
authors.lastname: Viriot
authors.forename: Joachim
authors.initials: J
authors.lastname: Herz
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
mesh_terms: D000565:Ameloblasts / Q000502:physiology; D000818:Animals; D005075:Biological Evolution; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003743:Dental Enamel / Q000648:ultrastructure; D003804:Dentin / Q000648:ultrastructure; D005399:Fishes / Q000033:anatomy & histology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007180:Incisor / Q000033:anatomy & histology / Q000502:physiology; D026502:LDL-Receptor Related Proteins; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D009805:Odontogenesis / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014071:Tooth Abnormalities / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D026502:LDL-Receptor Related Proteins; C116415:Lrp4 protein, mouse; D011973:Receptors, LDL; C465570:Shh protein, mouse