Chem. Senses 27: 445-451,
2002
© Oxford University Press 2002
The Neural Differentiation Gene Mash-1 has a Distinct Pattern of Expression from the Taste Reception-related Genes gustducin and T1R2 in the Taste Buds
1 National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan 2 Bio-oriented Technology Research Advancement Institution, 1-40-2 Nisshin-cho, Oomiya Saitama 331-0044, Japan 3 Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Correspondence to be sent to: Yuko Kusakabe, National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. e-mail: ykusa{at}nfri.affrc.go.jp
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Abstract |
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Taste bud cells have a limited lifespan and are continuously replaced just like other epithelial cells. Although there is some evidence that taste buds may arise from the local epithelium, taste receptor cells have neuronal properties. This implies that there must be a critical stage at which the epithelial precursor cells for taste receptor cells start to exhibit neural properties during the differentiation of the taste receptor cells. The expression of the neural-specific transcription factors Mash-1 and Prox-1 in the nervous system is transient and precedes neuronal differentiation. Therefore, we examined the expression of Mash-1 and Prox-1 in the epithelium of circumvallate papillae of the tongue in order to clarify the localization of the precursor cells with neural properties and observed that both expressions are restricted to the taste buds. Two-colour in situ hybridization showed that the signals for Mash-1 did not overlap those for taste receptor cell-specific genes such as gustducin and T1R2. In the process of development and regeneration of the taste buds, the expression of Mash-1 preceded that of gustducin and T1R2. These observations suggest that Mash-1 could be a candidate for a marker of immature taste receptor cells, including the cells that express gustducin and/or T1R2 at a later stage.
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Taste buds are sensory end organs that are composed of 50-150 cells and the maintenance of their morphology is dependent on innervation by gustatory fibres of the chorda tympani (VIIth) and glossopharyngea (IXth). It is known that taste bud cells are endodermal in origin (Barlow and Northcutt, 1995
),
that they have a limited lifespan and that they are continuously replaced in
the manner of other epithelial cells
(Beidler and Smallman, 1965;
Farbman, 1980;
Delay et al., 1986).
In particular, a study on the tongues of X chromosome-inactivation mosaic mice
suggested that the taste bud cells and epithelial cells around the taste buds
arose from a common progenitor and that the taste bud cells originated from
local tissue elements (Stone et
al., 1995). Our previous study showed that Patched 1, a
conserved target of sonic hedgehog, is expressed in the proliferating cells
around the taste buds and that denervation causes the loss of Patched 1
expression, thereby providing the first example of a denervation-induced
change in gene expression in the proliferating zone around the taste buds
(Miura et al.,
2001).
A taste bud might contain the cells in various stages of maturation. It is
assumed that, in aged taste bud cells, there might be an apoptotic cell death
pathway that mediates the apoptotic death factors P53, Bax and Caspase-2
(Zeng and Oakley, 1999;
Zeng et al., 2000).
On the other hand, the existence of undifferentiated taste bud cells has been
suggested by morphological and physiological studies
(Delay et al., 1986;
Mackay-Sim et al.,
1996), although no molecular marker has yet been found. In this
study we hypothesized that a phase in which the precursor for taste receptor
cells acquires the features of neural precursor cells might be found in the
differentiation process of taste receptor cells from epithelial precursor
cells, since mature taste receptor cells show the characteristics of neuronal
cells that form synapses and release neurotransmitters and which are capable
of generating action potentials.
In order to identify the location of the neural precursorlike cells for
taste receptor cells in the epithelium of the tongue, we here focus on the two
genes Mash-1 and Prox-1, which are related to the
development of the central nervous system (CNS). Mash-1 is a
mammalian homologue of the proneural genes of the Drosophila
achaete—scute complex (AS—C), which encodes a basic
helix—loop—helix (bHLH)-type transcription factor
(Johnson et al.,
1990). Mash-1 has been found to be expressed in the
developing peripheral nervous system (PNS) and CNS
(Lo et al., 1991;
Guillemot et al.,
1993). Prox-1, which is also expressed in the developing
brain, encodes a homeobox protein that is structurally homologous to
Drosophila prospero (Oliver
et al., 1993). Both Mash-1 and Prox-1
are defined as molecular markers for transient precursors in the CNS
(Torii et al., 1999).
Mash-1 expression was recently investigated in round cells in the
basal compartment of rat taste buds using in situ reverse
transcriptase polymerase chain reaction (in situ RT-PCR)
(Seta et al., 1999)
and, in cavefish, Prox-1 was found in the developing taste buds, as
well as the lens and retina (Jeffery
et al., 2000). However, the precise localization of
Mash-1 and Prox-1 expression in the epithelium of the tongue
is still poorly understood. Here we report that the expression of
Mash-1 and Prox-1 was restricted to the taste buds and that
the signals for Mash-1 did not overlap those for gustducin
(McLaughlin et al.,
1992) and T1R2 (Hoon
et al., 1999), which are the molecules related to taste
signal transduction.
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Materials and methods |
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Experimental animals
The adult animals used in this study were C57BL/6N mice of 8-20 weeks old.
The animals were initially purchased from Charles River Japan Inc. (Yokohama,
Japan) and were bred at National Food Research Institute. Timed pregnant
female mice were also purchased from Charles River Japan Inc. Embryonic day
0.5 (E0.5) was defined as the day on which the vaginal plug was
found and postnatal day 0 (P0) was designated as the day of birth.
The surgery for the glossopharyngeal (IXth) nerve crushes was performed as
described previously (Miura et
al., 2001). Adult mice were intraperitoneally anaesthetized
with Nembutal (50 mg/kg body weight) (Dainabot Co., Ltd., Osaka, Japan) and we
followed the guidelines of our institute for the care and use of experimental
animals.
Anti-sense RNA probes for in situ hybridization
cDNA fragments of Mash-1, Prox-1, gustducin and T1R2 were cloned by RT-PCR using the total RNA extracted from the epithelium of the circumvallate papillae and E13.5 brain and then used for synthesis of cRNA probes. The sequences of the primers were 5'-CGACAGTTTGGCCCGGCATGGAGA-3' (+59 to +82) and 5'-CCTGGCAGGT CCTCAGAACCAGTT-3' (+783 to +760) (Genbank M95603) for Mash-1 and 5'-ATGGGAAGTGGAATTAGTTC-3' (+114 to +133) and 5'-TCAGAAGAGCCCACAGTCTT-3' (+1178 to +1159) (Genbank X65747) for gustducin. Prox-1 and T1R2 were cloned using nested PCR. The primer sequences for the first PCR were as follows: Prox-1 5'-ATGCCTGACCATGACAGCACA-3' (+68 to +88) and 5'-CTACTCGTGAAGGAGTTCTTG-3' (+2281 to +2261) (Genbank AF061576) and T1R2 5'-TTCGCCGTGGAGGAAATCAA-3' (269+ to +288) and 5'-GAAGGAGAAGGTCATGCTGA-3' (2353+ to +2334) (Genbank NM_031873). The primer sequences for the second PCR were as follows: Prox-1 5'-TCTTAAGCCGGCAAACCAAGA-3' (+93 to +113) and 5'-TAGGCAGTTAGGGGATTTGAA-3' (+2260 to +2240) and T1R2 5'-AACTGTAGCTCTCTGCTGCC-3' (290+ to +309) and 5'-GTGATGAACTTGGCTTCGTT-3' (2331+ to +2312). The PCR was carried out for 40 cycles under the following conditions: 94°C for 1 min, 55°C for 1 min and 72°C for 2 min. Each resulting fragment was cloned into a pGEM-T easy vector (Promega Co., Madison, WI) and sequenced. Digoxygenin-UTP-labelled or fluorescein-UTP-labelled RNA probes were synthesized using an RNA transcription kit (Roche Diagnostics, Mannheim, Germany).
In situ hybridization
The mouse tongues were dissected, embedded in OCT compound (Sakura
Finetech. U.S.A., Inc., LosAngeles, CA), frozen in liquid nitrogen and
sectioned into 5 µm slices. In situ hybridization was performed as
described previously (Asano-Miyoshi et
al., 1998) and two-colour in situ hybridization
experiments were carried out under the same conditions with the following
modifications. The sections of circumvallate papillae were hybridized to both
digoxigenin-labelled and fluorescein-labelled cRNA probes. Following
hybridization and washing with 0.2 x SSC, the sections were incubated
with alkaline phosphatase-conjugated anti-fluorescein or anti-digoxigenin
antibodies (1:400 for 1 h at room temperature) (Roche Diagnostics), washed
with TBS (100 mM Tris—HCl, pH 7.5, 150 mM NaCl) and treated with
2-hydroxy-3-naphthoic acid-2'-phenylanilidephosphate (HNPP)/Fast Red
alkaline phosphatase substrate (Roche Diagnostics). The signals were observed
by fluorescence microscopy. After treatment with 0.1 M glycine, pH 2.2, with
0.1% Tween-20 for inactivating alkaline phosphatase activity, the sections
were re-fixed with 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.0,
washed with phosphate-buffered saline (137 mM NaCl, 2.7 mM KCl, 4.3 mM
Na2HPO4 and 1.4 mM KH2PO4) and
incubated with alkaline phosphatase-conjugated anti-fluorescein or
anti-digoxigenin antibodies (1:400) (Roche Diagnostics) overnight at 4°C.
After washing the sections with TBS, the colour reaction was performed with
1.5 mg/ml nitoroblue tetrazolium (NBT) and 0.75 mg/ml
5-bromo-4-chloro-3-indolyl phosphate (BCIP) in alkaline phosphatase buffer
(100 mM Tris—HCl, pH 9.5, 100 mM NaCl and 50 mM MgCl2)
overnight at room temperature. The HNPP/Fast Red signals were removed using an
alcohol dehydration step and then the NBT/BCIP signals were observed by light
microscopy. The images for HNPP/Fast Red and NBT/BCIP were overlaid by mean of
the program Photoshop® (Adobe Systems Inc., San Jose, CA). The numbers of
Mash-1+ cells and gustducin and T1 R2 (Ggust/T1
R2)+ cells were counted in the same section, averaged and represented
graphically. Statistical analysis was performed using paired
t-tests.
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Results |
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Expression of Mash-1 and Prox-1 is restricted to the taste buds in adult mice
In order to determine whether the neural precursor-like cells are located in the taste buds, we carried out in situ hybridization in the mouse circumvallate papillae with the Mash-1 and Prox-1 probes. A taste bud consists of elongated cells and round-shaped cells and it is known that localization of the round-shaped cells is restricted to the basal side of a taste bud. The signals for Mash-1 were mainly observed in a subset of the elongated taste bud cells (Figure 1A). Strong signals for Prox-1 were observed in a limited number of the round-shaped basal cells of the taste buds. On the other hand, moderate and diffuse signals were observed in the elongated cells (Figure 1B). The taste buds appeared to contain a greater number of Prox-1+ cells than Mash-1+ cells. We next used two-colour in situ hybridization for determining whether or not Mash-1 was expressed in the taste receptor cells. We used a mixed cRNA probe of T1 R2 and gustducin (Ggust/T1 R2) in order to detect the mature taste receptor cells. Two-colour in situ hybridization showed that both Mash-1 and Ggust/T1 R2 cRNA probes were detected in a subset of the taste bud cells but, interestingly, Mash-1+ cells did not overlap Ggust/T1 R2+ cells (Figure 2). The intensity of the signals in the elongated taste bud cells against Prox-1 was not sufficiently pronounced for detection with HNPP/Fast Red for two-colour in situ hybridization.
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Mash-1 and Prox-1 expression precedes Ggust/T1R2 expression during taste bud development
In order to ascertain whether Mash-1 was expressed earlier than taste receptors in the taste bud development, two-colour in situ hybridization with Mash-1 and Ggust/T1 R2 probes was carried out in P0.5 adult circumvallate papillae. At P0.5, when discernible taste buds were rarely observed, Mash-1+ cells were distributed in the centre of the circumvallate papillary epithelium and circumvallate trench (Figure 3A). The number of Mash-1+ cells was significantly larger than that of Ggust/T1 R2+ cells from P0.5 to P4.5 (Figures 3C,G,K and 4). The number of Ggust/T1 R2+ cells was more rapidly increased than that of Mash-1+ cells. The numbers of Mash-1+ cells and Ggust/T1 R2+ cells were approximately equal at P10.5 and the number of Mash-1+ cells was smaller than that of Ggust/T1 R2+ cells at adulthood (Figure 4). Mash-1+ cells did not overlap Ggust/T1 R2+ cells at any stage (Figure 3 C,G,K,O,R).
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Signals for Prox-1 were also observed by in situ hybridization before taste bud formation (Figure 3D,H,L). Prox-1 was expressed in the centre of the circumvallate papillary epithelium and circumvallate trench cells at P0.5 (Figure 3D) and in the trench cells between P2.5 and P4.5 (Figure 3H,L).
Mash-1 is expressed at the early stage of taste bud regeneration
We also examined the expression of Mash-1 and taste receptors
during the regeneration of taste buds. In a previous study the expression of
neural cell adhesion molecule (NCAM) after the crash of bilateral IXth nerves
showed that regeneration of the taste buds proceeds from the 10-12 days after
the nerve crush and that the taste buds are nearly normal in appearance by 20
days (Smith et al.,
1994). We therefore carried out two-colour in situ
hybridization with the Mash-1 and Ggust/T1 R2 probes using
the sections of circumvallate papillae at 11 days after the nerve crash for
the early stage and those at 16 days for the late stage of regeneration
(Figure 5A). Although there was
no discernible taste bud at 11 days after the nerve crush, Mash-1+
cells were seen in the epithelium while Ggust/T1 R2+ cells were not
observed. At 16 days after the operation, when a few taste buds had become
detectable, both Mash-1 and Ggust/T1 R2 were expressed in
the taste buds and the number of Mash-1+ cells was larger than the
number of Ggust/T1 R2+ cells
(Figure 5B).
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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In this study we found that Mash-1 was expressed in a subset of taste bud cells. Based on this finding, we will now discuss the characteristics of Mash-1+ cells. Mash-1+ cells in the CNS are defined as a transient proliferating population that is molecularly distinct from self-renewing stem cells and induction of Mash-1 might be one of the critical molecular events that control early development in the CNS (Torii et al., 1999
). Our results showed that, during the generation and
regeneration of taste buds, the expression of Mash-1 in non-elongated
cells was observed in the epithelium of circumvallate papillae prior to the
formation of taste buds and the expression of gustducin and
T1R2. The morphology of the non-elongated cells is similar to that of
the cells expressing Protein gene-product 9.5, neuron-specific enolase and
NCAM in the apical epithelium during early development of the taste buds
(Takeda et al., 1992;
Wakisaka et al.,
1996). Although morphological studies are needed for determining
the property of the non-elongated cells that express Mash-1 and/or
these proteins, the non-elongated cells are expected to be confined to the
elongated taste bud cells since the expression of Mash-1 and these
proteins is restricted to the taste buds in adult circumvallate papillae.
We also showed that Mash-1+ cells consistently failed to overlap
Ggust/T1R2+ cells from P0.5. It has been reported that
there are two taste receptor families in the mammalian tongue, namely T1Rs and
T2Rs and that the members of T1Rs, namely T1R2 and T1R3 and T2Rs are expressed
in a subset of the taste bud cells of circumvallate papillae
(Hoon et al., 1999;
Adler et al., 2000;
Kitagawa et al.,
2001; Max et al.,
2001; Montmayeur et
al., 2001; Nelson et
al., 2001; Sainz et
al., 2001). T1R2+ cells in circumvallate papillae
express T1R3 (Montmayeur et
al., 2001) and T2Rs+ cells express
gustducin, which is a taste bud-specific G protein related to sweet
and bitter taste signal transduction (Adler
et al., 2000). In addition, T1R2+ cells and
gustducin+ cells represent separate populations
(Hoon et al., 1999).
Taking these data from recent studies into consideration, Ggust/T1R2+
cells express the taste receptors T1R2, T1R3 or T2Rs and are
regarded as mature taste receptor cells that receive taste stimuli and form
synapses with gustatory nerve fibres and are electrically excitable as neural
cells, thereby indicating the possibility that Mash-1+ cells are not
mature taste receptor cells. If the role of Mash-1 in the turnover of
adult taste bud cells is not different from that in the development and
regeneration of taste buds, our results raise the possibility that
Mash-1 might be involved in the differentiation of taste receptor
cells and expressed transiently before the expression of taste receptors.
The cellular localization of Mash-1+ cells in the epithelium of
circumvallate papillae might reveal the point at which taste bud cells arisen
from the local epithelium start to display their neural characteristics in the
taste receptor cell lineage. The previous finding that
[3H]thymidine or Brd-U is incorporated during cell division
indicates that proliferating cells might not exist in the taste buds but in
the region around the taste buds. In this case a part of the proliferation
cells would migrate into the taste buds and finally gave rise to elongated
taste receptor cells (Beidler and Smallman,
1965; Cho et al.,
1998). Our previous study suggested that the proliferating cells
around the taste buds expressed Patched 1 depending on innervation
and that Patched 1+ cells were not present in taste buds
(Miura et al., 2001).
In the present study we showed that Mash-1 was expressed only in
taste bud cells, but not expressed in proliferation cells around the taste
buds, while in a previous study a fraction of Mash-1+ cells was
mainly observed in proliferating cells in the developing forebrain
neuroepithelium (Torii et al.,
1999). Our results lead us to a speculate that, when the property
of the precursor cells around the taste buds is switched from epithelial to
neuronal, the cells might stop their proliferation, enter the taste buds and
become transient neuronal precursor cells that are defined by the expression
of Mash-1. We observed that the expression of Mash-1 in
adult taste buds was mainly in elongated cells, suggesting that elongated
taste bud cells also include immature taste receptor cells that are at the
stage at which the cells undergo their final division and might begin to
differentiate into taste receptor cells with the properties of neurons. On the
other hand, Seta et al.
(1999) showed that
Mash-1 was only expressed in round-shaped cells in the basal
compartment, which had previously appeared to be basal cells in the taste
buds. We cannot deny the possibility that Mash-1 is also expressed in
the basal cells since they are considered to give rise to mature cells
(Naga et al., 1970),
but our result showed that the expression in round cells was not predominant.
More morphological studies are required in order to determine whether
Mash-1 is or is not expressed in round-shaped cells.
Both Mash-1 and Prox-1 were expressed at
P0.5-P4.5 and were expressed earlier than
Ggust/T1R2. Prox-1 is regarded as a molecular marker for transient
precursors in the developing CNS (Torii
et al., 1999), supporting the idea that not only
Mash-1 but also Prox-1 might play a role in the
differentiation of taste receptor cells. The strong signal for Prox-1
in adult taste buds in the present study was observed in round-shaped cells
and the weak one was observed in elongated cells. The number of
Prox-1+ elongated cells appeared to be much larger than the number of
Mash-1+ cells, thereby increasing the probability that
Prox-1+ elongated cells could overlap both Mash-1+ cells and
Ggust/T1R2+ cells. Two-colour in situ hybridization using
Prox-1, Mash-1 and Ggust/T1R2 probes could determine whether
Prox-1+ cells overlap with Mash-1+ cells and/or
Ggust/T1R2+ cells, but the signal for Prox-1 in this study
was too weak for determining cellular localization by two-colour in
situ hybridization. In a recent study, forced expression of
Mash-1 in a stem cell-derived cell line suggested that
Mash-1 functions upstream of Prox-1, which is consistent
with results on spatial and temporal expression in the developing CNS
(Torii et al., 1999).
In the case that Mash-1 leads to the expression of Prox-1 in
taste bud cells, our results raise the possibility that Prox-1 might
be expressed from the Mash-1+ stage to the Ggust/T1R2+ stage
during taste receptor cell differentiation. Culturing of stem cells for taste
bud cells will need to be performed in order to confirm this idea. The
possibility that Prox-1+ round-shaped cells could be the basal cells
differentiated into taste receptor cells and share the cell lineage with
Prox-1+ elongated cells should be tested in the same way.
Taste receptor cells are classified into different groups depending on the
expression of the taste receptors, e.g. T2Rs+ cells, T1R2+
cells and so on. Is Mash-1 expressed in precursor cells for all
groups of taste receptor cells? In our study no cells showed co-expression of
Mash-1 and Ggust/T1R2. This result leaves the question of
whether or not Mash-1+ cells mature to express gustducin
and/or T1R2 unanswered. However, in the olfactory receptor system,
despite the fact that individual olfactory receptor neurons are thought to
express one of the 1000 odorant receptor genes, Mash-1 is essential
for the differentiation of almost all receptor neurons
(Guillemot et al.,
1993), thereby supporting our speculation that Mash-1
might play a role in taste receptor cell differentiation and might be defined
as a marker for immature taste receptor cells.
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Acknowledgments |
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We thank Koji Naito for providing the experimental animals. This work was supported by a grant-in-aid from the Program for Promotion of Basic Research Activities for Innovation Bioscience at Bio-oriented Technology Research Advancement Institution. Yuko Kusakabe and Hirohito Miura contributed equally to this work.
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References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Adler, E., Hoon, M.A., Mueller, K.L., Chandrashekar, J., Ryba, N.J. and Zuker, C.S. (2000) A novel family of mammalian taste receptors. Cell,100 , 693-702.[Web of Science][Medline]
Asano-Miyoshi, M., Kusakabe, Y., Abe, K. and Emori Y.
(1998) Identification of taste-tissue-specific cDNA clones
from a subtraction cDNA library of rat circumvallate and foliate
papillae. J. Biochem. (Tokyo), 124,927
-933.
Barlow, L.A. and Northcutt, R.G. (1995) Embryonic origin of amphibian taste buds. Dev. Biol.,169 , 273-285.[Web of Science][Medline]
Beidler, L.M. and Smallman, R.L. (1965)
Renewal of cells within taste buds. J. Cell Biol.,27
, 263-272.
Cho, Y.K., Farbman, A.I. and Smith, D.V.
(1998) The timing of alphagustducin expression during cell
renewal in rat vallate taste buds. Chem. Senses,23
, 735-742.
Delay, R.J., Kinnamon, J.C. and Roper, S.D. (1986) Ultrastructure of mouse vallate taste buds: II. Cell types and cell lineage. J. Comp. Neurol.,253 , 242-252.[Web of Science][Medline]
Farbman, A.I. (1980) Renewal of taste bud cells in rat circumvallate papillae. Cell Tissue Kinet.,13 , 349-357.[Web of Science][Medline]
Guillemot, F., Lo, L.C., Johnson, J.E., Auerbach, A., Anderson, D.J. and Joyner, A.L. (1993) Mammalian achaete—scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell,75 , 463-476.[Web of Science][Medline]
Hoon, M.A., Adler, E., Lindemeier, J., Battey, J.F., Ryba, N.J. and Zuker, C.S. (1999) Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell, 96,541 -551.[Web of Science][Medline]
Jeffery, W., Strickler, A., Guiney, S., Heyser, D. and Tomarev, S. (2000) Prox 1 in eye degeneration and sensory organ compensation during development and evolution of the cavefish Astyanax. Dev. Genes Evol.,210 , 223-230.[Web of Science][Medline]
Johnson, J.E., Birren, S.J. and Anderson, D.J. (1990) Two rat homologues of Drosophila achaete—scute specifically expressed in neuronal precursors.Nature , 346,858 -861.[Medline]
Kitagawa, M., Kusakabe, Y., Miura, H., Ninomiya, Y. and Hino, A. (2001) Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem. Biophys. Res. Commun., 283,236 -242.[Web of Science][Medline]
Lo, L.C., Johnson, J.E., Wuenschell, C.W., Saito, T. and
Anderson, D.J. (1991) Mammalian
achaete—scute homolog 1 is transiently expressed by spatially
restricted subsets of early neuroepithelial and neural crest cells.Genes Dev.
, 5,1524
-1537.
Mackay-Sim, A., Delay, R.J., Roper, S.D. and Kinnamon, S.C. (1996) Development of voltage-dependent currents in taste receptor cells. J. Comp. Neurol.,365 , 278-288.[Web of Science][Medline]
Max, M., Shanker, Y.G., Huang, L., Rong, M., Liu, Z., Campagne, F., Weinstein, H., Damak, S. and Margolskee, R.F. (2001) Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat. Genet., 28,58 -63.[Web of Science][Medline]
McLaughlin, S.K., McKinnon, P.J. and Margolskee, R.F. (1992) Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature,357 , 563-569.[Medline]
Miura, H., Kusakabe, Y., Sugiyama, C., Kawamatsu, M., Ninomiya, Y., Motoyama, J. and Hino, A. (2001) Shh and Ptc are associated with taste bud maintenance in the adult mouse.Mech. Dev. , 106,143 -145.[Web of Science][Medline]
Montmayeur, J.P., Liberles, S.D., Matsunami, H. and Buck, L.B. (2001) A candidate taste receptor gene near a sweet taste locus. Nature Neurosci., 4,492 -498.[Web of Science][Medline]
Naga, I.A., Sakla, F.B., Girgis, Z.A. and State, F.A. (1970) Denervation of taste buds in the rabbit.Am. J. Anat. , 129,53 -63.[Web of Science][Medline]
Nelson, G., Hoon, M.A., Chandrashekar, J., Zhang, Y., Ryba, N.J. and Zuker, C.S. (2001) Mammalian sweet taste receptors. Cell, 106,381 -390.[Web of Science][Medline]
Oliver, G., Sosa-Pineda, B., Geisendorf, S., Spana, E.P., Doe, C.Q. and Gruss, P. (1993) Prox-1, a prospero-related homeobox gene expressed during mouse development.Mech. Dev. , 44,3 -16.[Web of Science][Medline]
Sainz, E., Korley, J.N., Battey, J.F. and Sullivan, S.L. (2001) Identification of a novel member of the T1R family of putative taste receptors. J. Neurochem.,77 , 896-903.[Web of Science][Medline]
Seta, Y., Toyono, T., Takeda, S. and Toyoshima, K. (1999) Expression of Mash1 in basal cells of rat circumvallate taste buds is dependent upon gustatory innervation.FEBS Lett. , 444,43 -46.[Web of Science][Medline]
Smith, D.V., Klevitsky, R., Akeson, R.A. and Shipley, M.T. (1994) Expression of the neural cell adhesion molecule (NCAM) and polysialic acid during taste bud degeneration and regeneration. J. Comp. Neurol.,347 , 187-196.[Web of Science][Medline]
Stone, L.M., Finger, T.E., Tam, P.P. and Tan, S.S.
(1995) Taste receptor cells arise from local epithelium, not
neurogenic ectoderm. Proc. Natl Acad. Sci. USA,92
, 1916-1920.
Takeda, M., Suzuki, Y., Obara, N. and Nagai, Y.
(1992) Neural cell adhesion molecule of taste buds.J. Electron Microsc.
(Tokyo), 41,375
-380.
Torii, M., Matsuzaki, F., Osumi, N., Kaibuchi, K., Nakamura, S., Casarosa, S., Guillemot, F. and Nakafuku, M. (1999) Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system. Development, 126,443 -456.[Abstract]
Wakisaka, S., Miyawaki, Y., Youn, S.H., Kato, J. and Kurisu, K. (1996) Protein gene-product 9.5 in developing mouse circumvallate papilla: comparison with neuron-specific enolase and calsitonin gene-related peptide. Anat. Embryol., 194,365 -372.[Medline]
Zeng, Q. and Oakley, B. (1999) p53 and Bax: putative death factors in taste cell turnover. J. Comp. Neurol., 413,168 -180.[Web of Science][Medline]
Zeng, Q., Kwan, A. and Oakley, B. (2000) Gustatory innervation and bax-dependent Caspase-2: participants in the life and death pathways of mouse taste receptor cells. J. Comp. Neurol., 424,640 -50.[Web of Science][Medline]
Accepted February 25, 2002
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