Abstract
Odontogenesis involves multiple events, including tissue-tissue interactions, cell proliferation, and cell differentiation, but the underlying mechanisms of regulation are far from clear. Because Fisp12/CTGF is a signaling protein involved in similar events in other systems, we asked whether it is expressed in developing tooth germs and what roles it may have. Indeed, Fisp12/CTGF transcripts were first expressed by dental laminas, invaginating epithelium, and condensing mesenchyme at the bud stage, and then became abundant in enamel knot and preameloblasts. Fisp12/CTGF was present not only in inner dental epithelium but also in stratum intermedium and underlying dental mesenchyme. Fisp12/CTGF expression decreased markedly in secreting ameloblasts. Tissue reconstitution experiments showed that Fisp12/CTGF expression in dental epithelium required interaction with mesenchyme but was maintained by treatment of epithelium with transforming growth factor-1, a factor regulating Fisp12/CTGF expression in other systems, or with bone morphogenetic protein-2. Loss-of-function studies using CTGF neutralizing antibodies revealed that interference with endogenous factor action in tooth germ explants led to a severe inhibition of proliferation in both epithelium and mesenchyme and a marked delay in cytodifferentiation of ameloblasts and odontoblasts. Treatment of dental epithelial and mesenchymal cells in culture with recombinant CTGF stimulated cell proliferation, whereas treatment with neutralizing antibodies inhibited it. The data demonstrate for the first time that Fisp12/CTGF is expressed during odontogenesis. Expression is confined to specific sites and times, is regulated by epithelial-mesenchymal interactions and critical soluble factors, and appears to be needed for proliferation and differentiation along both ameloblast and odontoblast cell lineages.
| Original language | English |
|---|---|
| Pages (from-to) | 267-278 |
| Number of pages | 12 |
| Journal | Developmental Dynamics |
| Volume | 224 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2002 |
| Externally published | Yes |
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Keywords
- Amelogenesis
- Connective tissue growth factor
- Epithelial-mesenchymal interactions
- Fisp12
- Tooth germ development
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
Cite this
Expression, gene regulation, and roles of Fisp12/CTGF in developing tooth germs. / Shimo, Tsuyoshi; Wu, Changshan; Billings, Paul C.; Piddington, Ronald; Rosenbloom, Joel; Pacifici, Maurizio; Koyama, Eiki.
In: Developmental Dynamics, Vol. 224, No. 3, 2002, p. 267-278.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression, gene regulation, and roles of Fisp12/CTGF in developing tooth germs
AU - Shimo, Tsuyoshi
AU - Wu, Changshan
AU - Billings, Paul C.
AU - Piddington, Ronald
AU - Rosenbloom, Joel
AU - Pacifici, Maurizio
AU - Koyama, Eiki
PY - 2002
Y1 - 2002
N2 - Odontogenesis involves multiple events, including tissue-tissue interactions, cell proliferation, and cell differentiation, but the underlying mechanisms of regulation are far from clear. Because Fisp12/CTGF is a signaling protein involved in similar events in other systems, we asked whether it is expressed in developing tooth germs and what roles it may have. Indeed, Fisp12/CTGF transcripts were first expressed by dental laminas, invaginating epithelium, and condensing mesenchyme at the bud stage, and then became abundant in enamel knot and preameloblasts. Fisp12/CTGF was present not only in inner dental epithelium but also in stratum intermedium and underlying dental mesenchyme. Fisp12/CTGF expression decreased markedly in secreting ameloblasts. Tissue reconstitution experiments showed that Fisp12/CTGF expression in dental epithelium required interaction with mesenchyme but was maintained by treatment of epithelium with transforming growth factor-1, a factor regulating Fisp12/CTGF expression in other systems, or with bone morphogenetic protein-2. Loss-of-function studies using CTGF neutralizing antibodies revealed that interference with endogenous factor action in tooth germ explants led to a severe inhibition of proliferation in both epithelium and mesenchyme and a marked delay in cytodifferentiation of ameloblasts and odontoblasts. Treatment of dental epithelial and mesenchymal cells in culture with recombinant CTGF stimulated cell proliferation, whereas treatment with neutralizing antibodies inhibited it. The data demonstrate for the first time that Fisp12/CTGF is expressed during odontogenesis. Expression is confined to specific sites and times, is regulated by epithelial-mesenchymal interactions and critical soluble factors, and appears to be needed for proliferation and differentiation along both ameloblast and odontoblast cell lineages.
AB - Odontogenesis involves multiple events, including tissue-tissue interactions, cell proliferation, and cell differentiation, but the underlying mechanisms of regulation are far from clear. Because Fisp12/CTGF is a signaling protein involved in similar events in other systems, we asked whether it is expressed in developing tooth germs and what roles it may have. Indeed, Fisp12/CTGF transcripts were first expressed by dental laminas, invaginating epithelium, and condensing mesenchyme at the bud stage, and then became abundant in enamel knot and preameloblasts. Fisp12/CTGF was present not only in inner dental epithelium but also in stratum intermedium and underlying dental mesenchyme. Fisp12/CTGF expression decreased markedly in secreting ameloblasts. Tissue reconstitution experiments showed that Fisp12/CTGF expression in dental epithelium required interaction with mesenchyme but was maintained by treatment of epithelium with transforming growth factor-1, a factor regulating Fisp12/CTGF expression in other systems, or with bone morphogenetic protein-2. Loss-of-function studies using CTGF neutralizing antibodies revealed that interference with endogenous factor action in tooth germ explants led to a severe inhibition of proliferation in both epithelium and mesenchyme and a marked delay in cytodifferentiation of ameloblasts and odontoblasts. Treatment of dental epithelial and mesenchymal cells in culture with recombinant CTGF stimulated cell proliferation, whereas treatment with neutralizing antibodies inhibited it. The data demonstrate for the first time that Fisp12/CTGF is expressed during odontogenesis. Expression is confined to specific sites and times, is regulated by epithelial-mesenchymal interactions and critical soluble factors, and appears to be needed for proliferation and differentiation along both ameloblast and odontoblast cell lineages.
KW - Amelogenesis
KW - Connective tissue growth factor
KW - Epithelial-mesenchymal interactions
KW - Fisp12
KW - Tooth germ development
UR - http://www.scopus.com/inward/record.url?scp=0035986548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035986548&partnerID=8YFLogxK
U2 - 10.1002/dvdy.10109
DO - 10.1002/dvdy.10109
M3 - Article
C2 - 12112457
AN - SCOPUS:0035986548
VL - 224
SP - 267
EP - 278
JO - Developmental Dynamics
JF - Developmental Dynamics
SN - 1058-8388
IS - 3
ER -