Follistatin Regulates Enamel Patterning in Mouse Incisors by Asymmetrically Inhibiting BMP Signaling and Ameloblast Differentiation

Wang, Xiu Ping; Suomalainen, Marika; Jorgez, Carolina J.; Matzuk, Martin M.; Werner, Sabine; Thesleff, Irma

doi:10.1016/j.devcel.2004.09.012

Cited by 182 publications

(227 citation statements)

References 45 publications

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“…BMP Signaling Has Been Shown to Induce Ameloblast Differentiation (15). We found Bmp4 and Bmp7 expression to be specifically downregulated in ameloblasts of Lrp4 hypo/hypo mutants at birth whereas expression was unaltered in odontoblasts ( Fig.…”

Section: Resultsmentioning

confidence: 69%

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Ohazama

Blackburn

Porntaveetus

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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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.V ertebrates exhibit remarkable diversity in their dentitions, which is a feature of the importance of tooth shape in adaptation to new feeding strategies in evolution. Even quite closely related species of mammals can have different shapes of teeth and thus tooth development provides an excellent model for molecularly based evolutionary developmental biological studies (evo/devo). These tooth evolutional changes took place by the activation or inactivation of gene function, and thus evolutionary lost structures or gene activation/inactivation during evolution are occasionally retained as vestigial structures or latent gene activation/inactivation at embryonic stages.The current view is that all mammalian teeth evolved from simple ancestral teeth with a conical shape not dissimilar to mammalian canines (1). Mammalian heterodont dentitions contain a variety of tooth shapes and most evo/devo studies have focused solely on the molar dentition, with cuspal morphology being used as the main comparative feature between specimens (1). A cusp is a pointed or rounded projection of the tooth that is composed of both enamel and dentin, and the general consensus is that multicuspid teeth (molariform) evolved from conical teeth by progressive addition of extra "cones" (1). Incisors however are a uniquely mammalian tooth type that are neither conical nor multicuspid and their evolutional process is not understood.Among mammalian teeth, murine dentition has been used as a powerful tool for evo/devo studies because of the relative ease of gene manipulation. A major defining feature of R...

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Section: Resultsmentioning

confidence: 69%

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Ohazama

Blackburn

Porntaveetus

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Numerous reports using gene targeting have shown that ablating function of BMP antagonists [Ectodin (Sostdc1, Wise) (49), Noggin (50), Osr2 (20)] increases tooth number. Similarly, ectopic expression of the BMP antagonist Follistatin, using the K14 promoter, reduces tooth number (51). BMP data for mammalian taste papillae are complicated and stage-specific.…”

Section: Discussionmentioning

confidence: 99%

Coevolutionary patterning of teeth and taste buds

Bloomquist

Parnell

Phillips

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium.quantitative trait loci | tooth/taste bud development | placode patterning | bipotency | plasticity

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“…The signals from the mesenchyme involved in the ameloblast induction include Bmp2, Bmp4, and Tgfb1 (Fig. 4) (Coin et al 1999;Wang et al 2004). In addition, Shh from the epithelial stratum intermedium cells is required to support ameloblast differentiation and maturation (Dassule et al 2000;Gritli-Linde et al 2002).…”

Section: Signaling Network Regulating Tooth Developmentmentioning

confidence: 99%

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

Jussila

Thesleff²

2012

Cold Spring Harbor Perspectives in Biology

225

209

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SUMMARYTeeth develop as ectodermal appendages from epithelial and mesenchymal tissues. Tooth organogenesis is regulated by an intricate network of cell -cell signaling during all steps of development. The dental hard tissues, dentin, enamel, and cementum, are formed by unique cell types whose differentiation is intimately linked with morphogenesis. During evolution the capacity for tooth replacement has been reduced in mammals, whereas teeth have acquired more complex shapes. Mammalian teeth contain stem cells but they may not provide a source for bioengineering of human teeth. Therefore it is likely that nondental cells will have to be reprogrammed for the purpose of clinical tooth regeneration. Obviously this will require understanding of the mechanisms of normal development. The signaling networks mediating the epithelial-mesenchymal interactions during morphogenesis are well characterized but the molecular signatures of the odontogenic tissues remain to be uncovered. Outline

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Follistatin Regulates Enamel Patterning in Mouse Incisors by Asymmetrically Inhibiting BMP Signaling and Ameloblast Differentiation

Cited by 182 publications

References 45 publications

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Coevolutionary patterning of teeth and taste buds

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

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