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First published online 1 March 2006
doi: 10.1242/dev.02307
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1 Department of Oral Anatomy and Developmental Biology, Osaka University
Graduate School of Dentistry, Osaka, Japan.
2 Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue
Regeneration and Reconstruction, Niigata University Graduate School of Medical
and Dental Sciences, Niigata, Japan.
3 Department of Oral Anatomy II, School of Dentistry, Iwate Medical University,
Morioka, Japan.
4 Department of Biological Science and Technology, Faculty of Engineering,
University of Tokushima, Tokushima, Japan.
* Author for correspondence (e-mail: hide-h{at}dent.osaka-u.ac.jp)
Accepted 2 February 2006
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MATERIALS AND METHODS
RESULTS
DISCUSSION
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Key words: Fibroblast growth factor 10, Apical bud, Inner enamel epithelium, Outer enamel epithelium, Hertwig's epithelial root sheath (HERS)
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MATERIALS AND METHODS
RESULTS
DISCUSSION
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;
Tucker and Sharpe, 2004).
These processes are regulated by the sequential and reciprocal interactions
between the oral ectoderm and the neural crest-derived mesenchyme, as well as
other ectodermal organs (Pispa and
Thesleff, 2003). Though several signaling pathways and
transcription factors have been implicated in the regulation of molar crown
development, relatively little is known about the regulatory mechanisms of
root development. It has recently been reported that NFI-C/CTF (nuclear factor
I-C/CAAT-box transcription factor) is essential for root or root analog
formation during tooth development
(Steele-Perkins et al., 2003).
Nfic-null mice exhibit the uniform lack of lower incisors.
Interestingly, despite forming the crown of molar and the crown analog of
upper incisors, the root and the root analog were defective in their teeth.
Furthermore, it has been speculated based on gene expression studies during
mouse molar root development that some growth factors, including bone
morphogenetic proteins (BMPs), epidermal growth factors (EGFs) and
transcriptional factors (i.e. Msx1, Msx2 and Runx2), are related to the growth
and differentiation of odontoblasts and/or cementoblasts, and the
mineralization of dentin and/or cementum
(Yamashiro et al., 2003). An
investigation of tooth phenotypes in follistatin knockout mice and of
transgenic mice overexpressing follistatin under the keratin 14 promoter
demonstrated that follistatin regulates the decision between the crown and
root analogs of incisors by asymmetrically inhibiting ameloblast
differentiation by antagonizing BMP signaling
(Wang et al., 2004a). It was
not clear, however, whether follistatin regulates this process during molar
development, as follistatin mRNA was not expressed in Hertwig's epithelial
root sheath (HERS) during root development
(Wang et al., 2004b).
In this study intended to elucidate the mechanism for the transition from
crown morphogenesis to the initiation of root formation, we focus on the
differential gene expression patterns of fibroblast growth factor (Fgf) 10
mRNA between continuously growing teeth and limited-growth teeth
(Fig. 1A). The former tooth
type has two continuously growing structures: the crown analog, consisting of
enamel and dentin (the labial side of mouse incisors), and the root analog,
consisting of dentin, cementum and the periodontal ligaments (lingual side).
The growth at the lingual side mimics the root development of mouse molar
germs (Fig. 1B,C). HERS and the
fragmented epithelium are visible at the lingual side of the apical end, and
periodontal ligaments are formed between the fragmented epithelium. In the
teeth, Fgf10, which is continuously expressed at the apical end of mouse
incisors (Fig. 1A)
(Harada et al., 1999), plays a
role in the maintenance of a dental epithelial stem cell compartment referred
to as `apical bud' (Harada et al.,
2002b; Harada and Ohshima,
2004). The apical bud is an epithelial bulge consisting of a basal
epithelium producing inner enamel epithelium (IEE), stellate reticulum and
outer enamel epithelium (OEE). The border between the basal epithelium, which
expresses lunatic fringe mRNA, and the stellate reticulum, which expresses
Notch1 mRNA in the apical bud, has been identified as the location of
dental epithelial stem cells (Harada et
al., 1999). Plural epithelial bulges show histological structures
similar to the apical buds in guinea pig molars, which are continuously
growing (Harada et al., 2002a;
Ohshima et al., 2005). In a
recent study, the constant expression of Fgf10 was also observed at
the apical ends of sibling vole molars, which are also continuously growing
(Fig. 1A)
(Tummers and Thesleff, 2003).
However, in mouse, rat and human molars, the expression of Fgf10
disappears when crown morphogenesis shifts to root formation
(Fig. 1A)
(Kettunen et al., 2000;
Tummers and Thesleff, 2003).
Neither histological structures (e.g. an apical bud) nor gene expression
patterns characteristic of a dental epithelial stem cell compartment is
observed in HERS during root development. In mouse molar germs, the
disappearance of Fgf10 signaling leads to the lack of a regulatory system for
the formation and maintenance of a dental stem cell compartment. Hence, to
clarify the relationship between root formation and the loss of a dental stem
cell compartment, we attempted to observe the growth of
Fgf10-deficient mouse incisors by transplanting them into the kidney
capsule. We have also examined the effects of transient Fgf10
overexpression during HERS formation in mouse molar germ cultures.
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MATERIALS AND METHODS
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).
Incisor germ transplantation
Incisor germs were dissected from the mandibles of
Fgf10+/+ or +/- and
Fgf10-/- mice at embryonic day 19 (E19). For
transplantation of the incisor germs, the apical end regions were mechanically
separated from the germs using an 18G needle
(Fig. 2). The regions were
transplanted underneath the kidney capsules of female mice (C57BL/6, PN w6),
allowed to incubate for 3 weeks and removed. Eighty percent of the explants
(wild type, 24; mutant, 16) grew well. The tissues were fixed in 4%
paraformaldehyde (PFA) in phosphate-buffered saline (PBS) (pH 7.2),
decalcified in 12.5% EDTA in PBS. For observation of translucent specimens,
the samples were treated with graded ethanol and acetone-ethanol, repeatedly.
For Hematoxylin and Eosin (HE) staining, the samples were dehydrated in graded
ethanol, embedded in paraffin wax and sectioned. For ultrastructural analysis,
the tissues were also fixed in 4% PFA + 2.5% glutaraldehyde in PBS (pH 7.2)
and decalcified in 12.5% EDTA in PBS. The samples were subsequently postfixed
in 1% OsO4 reduced with 1.5% potassium ferrocyanide, dehydrated in
an ascending series of ethanol and finally embedded in Epon 812 (Taab,
Berkshire, UK). Semi-thin sections (1 µm in thickness) were stained with
Toluidine Blue and ultra-thin sections (70 nm in thickness) were
double-stained with uranyl acetate and lead citrate, and examined with a
Hitachi H-7100 transmission electron microscope. For comparison with normal
root formation, the upper second molars of ICR mice at postnatal week three
(PN w3) were used.
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). Molar
germs (n=16) were dissected from the mandibles of ICR mice at
postnatal day 1 (PN d1). The vector pIRES2-ZsGreen1 (BD Biosciences-Clontech,
Palo Alto, CA, USA) containing the mFgf10 cDNA (kind gift from Prof.
Nobuyuki Itoh) was microinjected into the proximal dental papilla of the molar
germs using a Transjector5246 (Eppendorf, Hamburg, Germany) or transfected
using a BTX electroporation system T820 (voltage, 600 V; pulse, 30
µseconds; interval, 1 minute; three stimulations). The germs were cultured
for 5 days. Cells expressing Fgf10 protein were identified by detecting
ZsGreen1 fluorescence using a Keyence stereofluorescence microscope system
VB-G25 (Keyence, Osaka, Japan). To observe molar germ development, we used
samples (n=4) in which expression was restricted to the proximal
dental papilla.
Immunohistochemistry
We used unfixed 9 µm frozen sections for immunostaining. The sections
were incubated with mouse monoclonal anti-cytokeratin 14 (CK14, LL002,
NOVOCASTRA, Newcastle, UK) and rabbit anti-Notch2 (R&D Systems,
Minneapolis, MN, USA) antibodies for 2 hours at room temperature. Anti-mouse
VECTASTAIN ABC-kit (PK-6101, Vector Laboratories, Burlingame, CA, USA), donkey
anti-mouse antibody directly conjugated to Alexa488 (Invitrogen, Carlsbad, CA,
USA) and goat anti-rabbit antibody directly conjugated to Alexa546
(Invitrogen) were used as secondary antibodies.
Cell proliferation assays
We carried out 5'-bromo-2'-deoxyuridine (BrdU) labeling
analyses to detect cellular proliferation. To label the mutant incisors
growing under the kidney capsules, 1 mg/100 g (body weight) BrdU
(Sigma-Aldrich, St Louis, MO, USA) was injected into the abdominal cavity of
recipient mice (those transplanted with the mutant incisor germs), which were
sacrificed 2 hours later, at which point the incisor immunostaining was
carried out. In vitro cultures for observing root development of mouse molars
were performed as previously described
(Fujiwara et al., 2005).
Explants from PN d3 and d5 mice were incubated for 1 day and then washed with
Hanks' balanced salt solution in the presence of BrdU (0.5 mg/ml for 3 hours),
embedded in paraffin, and serially sectioned into 5 µm sections. BrdU was
detected on the sections using a BrdU staining kit (Calbiochem, Oncogene
Research Products, Cambridge, MA, USA) according to the manufacturer's
instructions, and visualized with streptavidin-HRP and DAB. BrdU-stained
specimens were then weakly counterstained with Hematoxylin. To compare the
mitotic activity between the inner and outer layers of the dental epithelium
in the mutant incisors and between the IEE and OEE in cultured molar germs, we
counted the number of BrdU-immunopositive cells and all cells in the inner and
outer layers and the dental papilla, and then estimated the mitotic index of
each. Dental epithelial cells were distinguished from mesenchymal cells by
CK14 immunostaining of serial sections.
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; Harada and Ohshima,
2004). Thus, even if the region is separated from the incisor
germ, the snippets are able to grow into parent incisors under the kidney
capsule. After the kidney was removed from the abdominal cavity of the
recipient three weeks after implantation, both wild-type and mutant incisors
were visible at the surface of the kidney
(Fig. 3C). The apical regions
of the teeth were covered by alveolar bone
(Fig. 3C, asterisk), and their
teeth erupted from sockets of bone. The mutant teeth were smaller than the
wild-type teeth. To observe the incisor structure, we prepared translucent
specimens (Fig. 3E-H) and HE
stained 4 µm sections (Fig.
3I,J). The translucent specimens were useful for three-dimensional
structural observations. In wild-type incisors, enamel and dentin were clearly
formed at the labial side. The apical bud, IEE and the related differentiated
ameloblasts were visible in the translucent specimens. The histological
structure of the wild-type incisors was similar to the parent incisor germs in
the mandibles of E19 mice. The differentiation of ameloblasts and odontoblasts
was normal. Enamel matrix was formed at the labial side, and dentin was
visible at both the labial and the lingual side. The related dental
epithelium, consisting of IEE, stratum intermedium, stellate reticulum and
OEE, was visible at the apical end. However, in the mutant incisors growing
under the kidney capsules, enamel was seen only in incisal end of the labial
side (Fig. 3F). The rest was
composed only of dentin. The epithelial layers of ameloblasts, IEE and the
apical bud were not observed at the surface of the enamel and dentin
(Fig. 3H,J). The features of
the labial side resembled the transitional region from crown to root as seen
in the mice molar. The border between crown and root was marked clearly, like
the cervical margin of molar teeth (Fig.
3H,J, red arrows). The surface of the enamel was covered with
dental epithelium consisting of cuboidal cells
(Fig. 3J, arrowheads); this
differed from secretory ameloblasts, which exhibit a tall and columnar shape
and produce enamel matrix. The epithelial layer was not clearly identifiable
at the surface of the dentin (Fig.
3J, arrows). Dentin formation and odontoblast differentiation were
normal.
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), we double stained for CK14 and Notch2 in the
mutant incisors (Fig. 4). The
results indicated that the epithelium expressed both CK14 and Notch2.
Immunostaining for Notch1, which is expressed by putative stem cells within
the apical bud and stratum intermedium, was not observed in the mutant
incisors (data not shown). Hence, it was likely that the epithelium was made
up of HERS and involved in the induction of root dentin formation.
Interestingly, Notch2 staining was observed in lingual epithelium
(Fig. 4J, larger arrow), as
well as in OEE and the stellate reticulum of the labial epithelium in
wild-type incisors (Fig. 4J,
smaller arrows).
Localization of proliferating cells at the initiation of HERS formation
To reconfirm the hypothesis that HERS originated from the stellate
reticulum and/or OEE, we examined the localization of the proliferating cells
at the initiation of HERS formation (Fig.
5D). To capture the precise environment surrounding the start of
HERS formation and its subsequent growth, we used an in vitro root culture
system (Fujiwara et al., 2005).
In vitro cultures are effective for BrdU labeling during a strict time frame,
because there is almost no time lag between the time of BrdU addition and
cellular uptake of the BrdU. The initiation of HERS formation was visible
after 1 day in the molar cultures of PN d3 mice, at which time the BrdU
labeling was carried out for 3 hours. BrdU-labeled cells were more apparent in
the OEE than in the IEE (Fig.
5D,G). The results were similar in the HERS of the cultures of PN
d5 mice (Fig. 5E,G). These
results showed that although IEE cells had nearly finished proliferating, the
OEE proliferated more actively. We were unsuccessful in our attempts to find a
similar situation in the mutant incisors growing under kidney capsules,
because the growth rate of the transplants was unstable and impossible to
control. However, BrdU labeling analyses in the epithelial sheaths of mutant
incisors also showed greater numbers of positive cells in the outer epithelium
than in the inner epithelium (Fig.
5A-C,F). These results were identical to those of a previous paper
demonstrating the proliferating cells of mouse molar HERS in in vitro cultures
(Fujiwara et al., 2005).
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Overexpression of Fgf10 leads to the formation of apical buds in molar germs
Finally, to determine whether Fgf10 expression inhibits the transition from
crown to root formation, we transiently overexpressed Fgf10 protein in the
lower first molar germs at PN d1. We monitored Fgf10 expression in the culture
of molar germs by the expression of green fluorescence protein ZsGreen1.
Before the experiments, we transfected the Fgf10 expression vector into HAT-7
cells (dental epithelial cell line), which do not express Fgf10, and
confirmed the co-expression of Fgf10 and ZsGreen1 by reverse transcription PCR
(data not shown). Next, the vector was transfected into the proximal dental
papilla cells of molar germs and the germs were cultured for 5 days. Cells
expressing Fgf10 protein were observed by green fluorescence only at the
proximal dental papilla 2 days after the transfection
(Fig. 7A, arrow), and further
extended along with the growth of the distal epithelium 3 days later
(Fig. 7B). The proximal dental
epithelium expanded to a greater extent than the distal epithelium
(Fig. 7C, arrow). Frozen
sections clearly showed the formation of epithelial bulges like apical buds of
mouse incisors (Fig. 7D, larger
arrow) and an expanded inter-cuspal epithelium
(Fig. 7D, arrowheads) following
Fgf10 expression. However, the distal epithelium (control side) formed the
HERS, consisting of two or three epithelial cell layers
(Fig. 7D, smaller arrow).
Because the transient expression of Fgf10 did not last beyond 1 week (data not
shown), we could not observe the effects on root formation of molar germs in
vitro or under the kidney capsule.
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DISCUSSION
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The stem cell compartment disturbs the transition from crown to root
The histological structure at the apical end of the labial dental
epithelium in mutant incisors is very similar to that of the cervical loop of
the molar germ, consisting of the IEE, stratum intermedium, stellate reticulum
and OEE. Our previous data from in vitro cultures suggested that incisors,
having no dental epithelial stem cells, lose the capacity for continuous
growth throughout life. However, we could not observe the in vitro formation
of dentin or periodontal tissues. Implantation into kidney capsules makes it
possible to mimic the growth of the mutant incisor germ in vivo. Our data show
that the mutant incisor germs form roots after completing crown formation at
the labial side. Accordingly, the Fgf10 deficiency causes the
defective apical bud and the formation of structures mimicking the cervical
loop of mouse molar germs, consequently leading to root formation. We
previously presented another example exhibiting continuous formation of a
crown analog (Harada, 2002a; Ohshima et
al., 2005). Guinea pig molars also had plural epithelial bulges
consisting of basal epithelium and stellate reticulum at the apical end. Taken
together, the apical bud-like structure of the stem cell compartment has the
capacity for constant production of ameloblasts, disturbing the transition
from crown to root.
Is Fgf10 a stimulating factor for crown formation and/or a negative regulator of root formation?
During molar development, when the dental epithelium initiates root
formation following the completion of crown morphogenesis, the expression of
Fgf10 in the dental papilla disappears
(Kettunen et al., 2000;
Tummers and Thesleff, 2003).
In incisor germ and vole molar germ, the expression of Fgf10 is not
observed at the region of root formation. However, continuous expression of
Fgf10 leads to continuous formation of crown analog in the continuous
growing teeth. Additionally, in our in vitro experiments, overexpression of
Fgf10 resulted in the formation of epithelial bulges resembling
apical buds and the expansion of the inter-cuspal epithelium during molar
development. Based on these data, Fgf10 expression is closely
associated with the formation of the epithelial stem cell compartment.
Furthermore, it has been reported that Fgf10 plays a role in the production of
the stratum intermedium through the induction of proliferation and the
differentiation of the IEE (Kawano et al.,
2004). The stratum intermedium is seen only at the proximal side
of the IEE and differentiated ameloblasts during crown formation, but not in
the root analog. These results suggest that Fgf10 signaling is required for
both the formation of the tooth crown and the maintenance of the stem cell
compartment. Conversely, it could be that Fgf10 inhibits the transition from
crown formation to root development. However, two events related to these
processes are paradoxical. First, why, despite Fgf10 expression around the
HERS-like epithelial sheath at the lingual side, is crown analog not formed at
the lingual side of mouse incisors? Wang and colleagues addressed this problem
using follistatin knockout mice and transgenic mice overexpressing follistatin
under the keratin 14 promoter (Wang et
al., 2004b). Follistatin, when expressed in the lingual
epithelium, inhibits the differentiation of ameloblasts by antagonizing BMPs
and disturbing enamel formation. Follistatin may also be a negative regulatory
factor in the selection of crown formation. Second, why does Fgf3, when
expressed in the mesenchyme adherent to the labial dental epithelium, not
rescue the continuous formation of crown analog in mutant incisors? The
deficiency of Fgf10 signaling leads to the lack of a stem cell compartment,
because expression of Fgf3 is not seen in the mesenchyme around the
apical bud (Harada et al.,
2002b). Accordingly, as previously described, even if the IEE can
proliferate and differentiate in response to Fgf3 before birth, the IEE
exhibits limited growth, as it is composed of transit amplifying cells. It
follows that the root formation of mutant incisors is due to the lack of a
dental epithelial stem cell compartment. During molar development, the
disappearance of Fgf10 causes the cessation of crown formation
without the formation of a stem cell compartment.
Transition processes between crown morphogenesis and root development
Based on these results, we consider mechanisms for the transition from
crown morphogenesis to root formation during the following three processes in
mutant incisors: (1) cessation of IEE growth, (2) formation of HERS, and (3)
fragmentation of dental epithelium. Previous studies using in vitro cultures
have shown that the growth of mutant incisors decreases gradually and then
stops (Harada et al., 2002b).
Therefore, the IEE cells stop proliferating after several cell divisions and
become differentiated ameloblasts. During molar development, ameloblasts do
not exhibit proliferative activity after the IEE molds the crown morphology.
Taken together, the termination of cell division and differentiation of IEE
cells is one of the most important events in the transition from crown to root
development.
Second, how is the HERS of molars or mutant incisors produced? The IEE and
OEE have been thought to fuse below the level of the crown cervical margin.
However, little evidence has supported this hypothesis.
Fig. 5 shows that BrdU-labeled
cells are observed in the OEE to a much greater degree than in the IEE at the
initiation of HERS formation. During the following stage, the outer layer of
the HERS preferentially proliferates in both the mouse molars and the mutant
incisors. A recent paper reported that insulin-like growth factor (IGF) 1, a
signaling molecule produced by dental follicles, induces the proliferation of
HERS during root development (Fujiwara et
al., 2005); the dental follicle cells then migrate downwards in
coordination with the elongation of the OEE
(Diekwisch, 2002). Furthermore,
Notch2 is expressed in the OEE and stellate reticulum during crown
development of molars and incisors, and in the HERS during molar root
development (Mitsiadis et al.,
1995; Harada et al.,
1999; Tummers and Thesleff,
2003). In this study, we show that the lingual epithelium of
wild-type incisors and the HERS of mutant incisors express Notch2 receptors
(Fig. 4). Taken together, we
hypothesize that the OEE proliferates more actively than the IEE and elongates
downwards below the crown cervical margin, producing a bilayered epithelial
sheath referred to as the HERS.
Third, immunostaining for CK14 shows that the fragmentation of the dental epithelial sheath, an important event in root development, occurs at the labial side in mutant mice. Additionally, electron microscopy shows cementum matrix deposition at the surface of the dentin and the formation of thick collagen bundles for the periodontal ligament. Consequently, these events during root development are also caused by the deficiency in Fgf10 signaling.
Based on our data and previous work, the disappearance of Fgf10 signaling
is key to the cessation of crown formation and the initiation of root
development. It is crucial to elucidate the molecular mechanisms regulating
the formation of both crown and root, as these mechanisms will contribute
greatly to our understanding of the evolution of tooth morphology and growth
patterns. The variety of Fgf10 expression patterns is thought to
facilitate the diversification of teeth: size, number of cusps and whether the
teeth are of continuous or limited growth. Recently, a cis-element was
identified that regulates Fgf10 expression during inner ear
development (Ohuchi et al.,
2005). However, the molecular mechanisms controlling the
expression of Fgf10 in teeth have not yet been elucidated and remain
the subject of future studies.
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ACKNOWLEDGMENTS |
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REFERENCES |
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TOP
SUMMARY
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES |
|---|
Diekwisch, T. G. H. (2002). Pathway and fate of
migratory cells during late tooth organogenesis. Connect. Tissue
Res. 43,245
-256.[Medline]
Fujiwara, N., Tabata, M. J., Endoh, M., Ishizeki, K. and Nawa,
T. (2005). Insulin-like growth factor-I stimulates cell
proliferation in the outer layer of Hertwig's epithelial root sheath and
elongate of the tooth in mouse molars in vitro. Cell Tissue
Res. 320,69
-75.[CrossRef][Medline]
Harada, H. and Ohshima, H. (2004). New
perspectives on tooth development and the dental stem cell niche.
Arch. Histol. Cytol. 67,1
-11.[CrossRef][Medline]
Harada, H., Kettunen, P., Jung, H.-S., Mustonen, T., Wang, Y. A.
and Thesleff, I. (1999). Localization of putative stem cells
in dental epithelium and their association with Notch and FGF signaling.
J. Cell Biol. 147,105
-120.
Harada, H., Mitsuyasu, T., Toyono, T. and Toyoshima, K.
(2002a). Epithelial stem cells in teeth.
Odontology 90,1
-6.[CrossRef][Medline]
Harada, H., Toyono, T., Toyoshima, K., Yamasaki, M., Itoh, N.,
Kato, S., Sekine, K. and Ohuchi, H. (2002b). FGF10 maintains
stem cell compartment in developing mouse incisors.
Development 129,1533
-1541.
Kawano, S., Saito, M., Handa, K., Morotomi, T., Toyono, T.,
Seta, Y., Nakamura, N., Uchida, T., Toyoshima, K., Ohishi, M. and Harada,
H. (2004). Characterization of dental epithelial progenitor
cells derived from cervical loop epithelium in rat lower incisor.
J. Dent. Res. 83,129
-133.
Kettunen, P., Laurikkala, J., Itaranta, P., Vainio, S., Itoh, N.
and Thesleff, I. (2000). Associations of FGF-3 and FGF-10
with signaling networks regulating tooth morphogenesis. Dev.
Dyn. 219,322
-332.[CrossRef][Medline]
Mitsiadis, T. A., Lardelli, M., Lendahl, U. and Thesleff, I.
(1995). Expression of Notch 1, 2 and 3 is regulated by
epithelial-mesenchymal interactions and retinoic acid in the developing mouse
tooth and associated with determination of ameloblast cell fate. J.
Cell Biol. 130,407
-418.
Ohshima, H., Nakasone, N., Hashimoto, E., Nakakura-Ohshima, K.
and Harada, H. (2005). The eternal tooth germ is formed at
the apical end of continuously growing teeth. Arch. Oral
Biol. 50,153
-157.[CrossRef][Medline]
Ohuchi, H., Yasue, A., Ono, K., Sasaoka, S., Tomonari, S.,
Takagi, A., Itakura, M., Moriyama, K., Noji, S. and Nohno, T.
(2005). Identification of cis-element regulating
expression of the mouse Fgf10 gene during inner ear development.
Dev. Dyn. 233,177
-187.[CrossRef][Medline]
Pispa, J. and Thesleff, I. (2003). Mechanisms
of ectodermal organogenesis. Dev. Biol.
262,195
-205.[CrossRef][Medline]
Salazar-Ciudad, I., Jernvall, J. and Newman, S. A.
(2003). Mechanisms of pattern formation in development and
evolution. Development
130,2027
-2037.
Sekine, K., Ohuchi, H., Fujiwara, M., Yamasaki, M., Yoshizawa,
T., Sato, T., Yagishita, N., Matsui, D., Koga, Y., Itoh, N. and Kato, S.
(1999). Fgf10 is essential for limb and lung formation.
Nat. Genet. 21,138
-141.[CrossRef][Medline]
Steele-Perkins, G., Butz, K. G., Lyons, G. E., Zeichner-David,
M., Kim, H.-J., Cho, M. I. and Gronostajski, R. M. (2003).
Essential role for NFI-C/CTF transcription-replication factor in tooth root
development. Mol. Cell. Biol.
23,1075
-1084.
Tucker, A. and Sharpe, P. (2004). The
cutting-edge of mammalian development; how the embryo makes teeth.
Nat. Rev. Genet. 5,499
-508.[Medline]
Tummers, M. and Thesleff, I. (2003). Root or
Crown: a developmental choice orchestrated by the differential regulation of
the epithelial stem cell niche in the tooth of two rodent species.
Development 130,1049
-1057.
Wang, X.-P., Suomalainen, M., Jorgez, C. J., Matzuk, M. M.,
Wankell, M., Werner, S. and Thesleff, I. (2004a). Modulation
of activin/bone morphogenetic protein signaling by follistatin is required for
the morphogenesis of mouse molar teeth. Dev. Dyn.231,98
-108.[CrossRef][Medline]
Wang, X.-P., Suomalainen, M., Jorgez, C. J., Matzuk, M. M.,
Werner, S. and Thesleff, I. (2004b). Follistatin regulates
enamel patterning in mouse incisors by asymmetrically inhibiting BMP signaling
and ameloblast differentiation. Dev. Cell
7, 719-730.[CrossRef][Medline]
Yamashiro, T., Tummers, M. and Thesleff, I.
(2003). Expression of bone morphogenetic proteins and Msx genes
during root formation. J. Dent. Res.
82,172
-176.
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  D.-S. Lee, J.-T. Park, H.-M. Kim, J. S. Ko, H.-H. Son, R. M. Gronostajski, M.-I. Cho, P.-H. Choung, and J.-C. Park Nuclear Factor I-C Is Essential for Odontogenic Cell Proliferation and Odontoblast Differentiation during Tooth Root Development J. Biol. Chem., June 19, 2009; 284(25): 17293 - 17303. [Abstract] [Full Text] [PDF]
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 K. Takamori, R. Hosokawa, X. Xu, X. Deng, P. Bringas Jr., and Y. Chai Epithelial Fibroblast Growth Factor Receptor 1 Regulates Enamel Formation Journal of Dental Research, March 1, 2008; 87(3): 238 - 243. [Abstract] [Full Text] [PDF]
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 O. D. Klein, D. B. Lyons, G. Balooch, G. W. Marshall, M. A. Basson, M. Peterka, T. Boran, R. Peterkova, and G. R. Martin An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors Development, January 15, 2008; 135(2): 377 - 385. [Abstract] [Full Text] [PDF]
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 J Buratini Jr., M.G.L Pinto, A.C Castilho, R.L Amorim, I.C Giometti, V.M Portela, E.S Nicola, and C.A Price Expression and Function of Fibroblast Growth Factor 10 and Its Receptor, Fibroblast Growth Factor Receptor 2B, in Bovine Follicles Biol Reprod, October 1, 2007; 77(4): 743 - 750. [Abstract] [Full Text] [PDF]
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