title: Morphoregulation of teeth: modulating the number, size, shape and differentiation by tuning Bmp activity.
abstract: During development and evolution, the morphology of ectodermal organs can be modulated so that an organism can adapt to different environments. We have proposed that morphoregulation can be achieved by simply tilting the balance of molecular activity. We test the principles by analyzing the effects of partial downregulation of Bmp signaling in oral and dental epithelia of the keratin 14-Noggin transgenic mouse. We observed a wide spectrum of tooth phenotypes. The dental formula changed from 1.0.0.3/1.0.0.3 to 1.0.0.2(1)/1.0.0.0. All mandibular and M3 maxillary molars were selectively lost because of the developmental block at the early bud stage. First and second maxillary molars were reduced in size, exhibited altered crown patterns, and failed to form multiple roots. In these mice, incisors were not transformed into molars. Histogenesis and differentiation of ameloblasts and odontoblasts in molars and incisors were abnormal. Lack of enamel caused misocclusion of incisors, leading to deformation and enlargement in size. Therefore, subtle differences in the level, distribution, and timing of signaling molecules can have major morphoregulatory consequences. Modulation of Bmp signaling exemplifies morphoregulation hypothesis: simple alteration of key signaling pathways can be used to transform a prototypical conical-shaped tooth into one with complex morphology. The involvement of related pathways and the implication of morphoregulation in tooth evolution are discussed.
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Maksim V
authors.initials: MV
authors.lastname: Plikus
authors.forename: Maggie
authors.initials: M
authors.lastname: Zeichner-David
authors.forename: Julie-Ann
authors.initials: JA
authors.lastname: Mayer
authors.forename: Julia
authors.initials: J
authors.lastname: Reyna
authors.forename: Pablo
authors.initials: P
authors.lastname: Bringas
authors.forename: J G M
authors.initials: JG
authors.lastname: Thewissen
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chuong
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D003743:Dental Enamel / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007180:Incisor / Q000196:embryology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008963:Molar / Q000196:embryology* / Q000648:ultrastructure; D009024:Morphogenesis; D009805:Odontogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein