Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Shh Signaling and Regulatory Gene Expression in Mouse Taste Buds
1 National Food Research Institute, 2 Asahi Breweries Ltd and 3 Kyushu University
Correspondence to be sent to: Hirohito Miura, e-mail; hmiura{at}affrc.go.jp
Key words: Mash1, Nkx2.2, Patched1 (Ptc), Sonic hedgehog (Shh), taste bud
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Introduction |
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 Top Introduction Shh signaling in taste...Regulatory genes in taste...AcknowledgementsReferences |
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In mammals, taste buds arise from local epithelium and are maintained by continuous cell renewal (Beidler and Smallman, 1965
;
Farbman, 1980;
Delay et al., 1986;
Stone et al., 1995). The
life span of taste cells is estimated to be ~10 days. Denervation causes the degeneration
of taste buds, indicating that the taste nerves trophically maintain the taste buds. It
is assumed that cell proliferation, differentiation and death for taste buds are
regulated in a coordinated fashion. However, the mechanism of each process in taste buds
remains to be clarified. |
Shh signaling in taste buds |
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TopIntroductionShh signaling in taste...Regulatory genes in taste...AcknowledgementsReferences |
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Sonic hedgehog (Shh) is an evolutionarily conserved intercellular signaling molecule and Patched1 (Ptc) is its receptor (Ingham and McMahon, 2001
). Shh signaling
is known to mediate various inductive events, including cell proliferation and
differentiation, in animal development. We have examined the expression of Shh
signaling-related genes in taste buds of adult mice. The expression of Shh was
found in the basal cells in taste buds, and Ptc expression was observed in the
surrounding region of the Shh expression (Figure
1;
Miura et al., 2001). This
Shh and Ptc expression pattern was observed in every taste papilla
(Figure
2). While Ptc expression
itself can indicate the tissues responding to Shh during development (Goodrich et al., 1996;
Marigo et al., 1996), the
expression of Shh target gene Gli1 was also observed in almost same
region where Ptc was expressed, indicating that the cells responded to
Shh signal (Figure
1). Analysis of BrdU incorporation
showed mitotic cells were observed mainly in Ptc-expressing region, while
mitotic cells in and around taste buds have been thought to contain the taste bud
progenitors (Beidler and Smallman,
1965;
Delay et al., 1986). In
addition, the expression of a downstream gene of Shh, Nkx2.2, was
observed in a subset of taste cells (Miura et
al., 2003). Nkx2.2 is a homeobox, which is induced by
Shh in the ventral region of neural tube and is required for the specification
of ventral neuron (Briscoe et al.,
2000). These data raise the possibility that Shh signal may be
involved in taste cell differentiation and that Nkx2.2-expressing cells in taste
buds might be derived from the Ptc-expressing cells, which received Shh
signal. The transection of cranial nerve IXth caused the rapid loss of Shh
expression in the basal cells in taste buds of circumvallate papillae, suggesting the
possible involvement of Shh signaling in the taste bud maintenance (Miura et al., 2001).
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Regulatory genes in taste buds and possible cell lineage |
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TopIntroductionShh signaling in taste...Regulatory genes in taste...AcknowledgementsReferences |
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On the other hand, most Nkx2.2-expressing taste cells co-expressed Mash1, a bHLH transcription factor required for neuronal differentiation in CNS and olfactory epithelium (OE) (Miura et al., 2003
). We have previously reported that, in taste buds, the
expression of Mash1 segregated with those of taste reception-related genes,
gustducin and T1r2, and that Mash1 expression preceded taste
reception-related gene expressions during development (Kusakabe et al., 2002). Based on these data, we
speculated that gustducin- and T1r2-expressing cells might be derived
from Mash1-expressing cells. The expression of NeuroD in
gustducin-expressing cells (Suzuki
et al., 2002) appears to be consistent with this idea by
consideration of the sequential expression of bHLH transcription factors in neuronal
differentiation in olfactory epithelium: Mash1 is expressed in the early phase,
and induces the expression of the other bHLH genes including NeuroD (Cau et al., 2002). Based on
ultrastructural characteristics, the taste bud cells have been categorized into four cell
types—basal cell, type I (dark) cell, type II cell and type III (light)
cell—and some immunohistochemical markers have been shown to correlate with each
cell types: gustducin and NCAM are specific for type II and type III,
respectively (Yee et al.,
2001). However, it is not clear whether these cell types represent separate
cell lineages or transient cell states of one cell lineage (Pumplin et al., 1997;
Delay et al., 1986). We found
almost of all Mash1-expressing taste cells were NCAM-positive (unpublished
data). Therefore, the hypothesis that gustducin-expressing cells derived from
Mash1-expressing cells proposes the possible cell lineage of type II cell from
type III cell. Mash1 and NeuroD are bHLH factors critical for neuronal
differentiation, while Type I cell has been considered as a glia-like cell (Lindemann, 1996;
Lawton et al., 2000).
Recently, the expression of the genes related to Delta-Notch signaling in taste buds has
been reported (Seta et al.,
2003). This signaling is known to be involved in neuron–glia cell fate
determination, and therefore it may be possible for the Delta-Notch signaling to be
involved in a cell-fate choice between neuron-like cell and glia-like cell in taste buds.
Our hypothesis of taste cell lineage is summarized schematically in Figure
3.
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Acknowledgements |
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TopIntroductionShh signaling in taste...Regulatory genes in taste...AcknowledgementsReferences |
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The authors thank Dr. Matthew P. Scott for providing with Ptc mutant mice. This study was supported by Bio-oriented Technology Research Advancement Institution.
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TopIntroductionShh signaling in taste...Regulatory genes in taste...AcknowledgementsReferences |
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