Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts.
Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin-null mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.
Fukumoto
Satoshi
S
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Kiba
Takayoshi
T
Hall
Bradford
B
Iehara
Noriyuki
N
Nakamura
Takashi
T
Longenecker
Glenn
G
Krebsbach
Paul H
PH
Nanci
Antonio
A
Kulkarni
Ashok B
AB
Yamada
Yoshihiko
Y
D000565:Ameloblasts / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003743:Dental Enamel / Q000002:abnormalities* / Q000378:metabolism*; D003746:Dental Enamel Proteins / Q000235:genetics* / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D014071:Tooth Abnormalities / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
C490890:Ambn protein, mouse; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D003746:Dental Enamel Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D011993:Recombinant Fusion Proteins