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#P124
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
Hedgehog-responding cells in taste papillae are progenitors of
lingual taste bud cells
Hong-Xiang Liu
1
, Alexandre Ermilov
2
, Andrzej Dlugosz
2,3
,
Charlotte M Mistretta
1
1
Department of Biologic and Materials Sciences, School of
Dentistry, University of Michigan Ann Arbor, MI, USA,
2
Department of Dermatology, Medical School, University of
Michigan Ann Arbor, MI, USA,
3
Department of Cell and
Developmental Biology, Medical School, University of Michigan
Ann Arbor, MI, USA
Sonic hedgehog (Shh) signaling regulates taste papilla
development. In adult mouse fungiform papilla, Shh is specifically
localized within taste buds. The transcription factor,
Gli1
, a reliable
reporter of hedgehog (Hh) signaling activity, is expressed primarily
in papilla epithelial cells that surround taste buds (but not within
taste buds), in basal cells of the papilla epithelium, and in a
population of mesenchymal cells in the papilla connective tissue
core. This suggests that Shh that is produced by taste cells may
signal to surrounding papilla cells for regulation of taste bud
maintenance. To investigate the roles of Hh-responding cells in the
maintenance of taste buds, we used a
Gli1-CreER
t2
/R26R
mouse
line for cell lineage tracing analysis. Tamoxifen injection was used
to induce
lacZ
gene expression in
Gli1
-expressing cells and derived
cells. Postnatal tongues were analyzed from 1 day to 3 months after
tamoxifen injection, with X-Gal staining in whole tongue followed
by cryostat sectioning. After tamoxifen injection, in addition to the
Gli1
-expressing cells described above, labeled cells are found
within taste buds. Taste buds are fully or partially labeled. Labeling
in taste bud cells is sustained at 3 months after tamoxifen injection
whereas label in the fungiform papilla epithelium disappears.
Immunoreactions for a pan-taste cell marker, Keratin 8,
demonstrated that the X-Gal labeled cells within taste buds are
K8 positive. Our results indicate that
Gli1
-expressing cells in the
papilla epithelium surrounding taste buds are progenitors of taste
cells, and that Hh signaling is important for the maintenance of
taste buds. Acknowledgements: NIH NIDCD Grant DC000456
(CMM) and NIAMS AR045973 (AAD)
#P125
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
Chemotherapy Drugs Induce Apoptosis and Decrease the
Number of Progenitor Cells in the Taste Epithelium
Amy Gowing, Pu Feng, Janice Chou, Jinghua Chai, Hong Wang
Monell Chemical Senses Center Philadelphia, PA, USA
Taste abnormalities associated with chemotherapy are contributing
factors toward development of food aversion and decreased caloric
intake in cancer patients. Previous studies reported that up to two
thirds of patients treated with chemotherapy experience taste
alterations. The goal of this study is to understand the underlying
mechanisms of chemotherapy-associated taste dysfunction.
We investigated the effects of three chemotherapeutic agents,
5-fluorouracil (5-FU), cisplatin, and paclitaxel (PTX), on peripheral
taste tissues. These drugs belong to different categories of
anticancer agents and have been reported to affect taste in cancer
patients. 5-FU (150 mg/kg), cisplatin (7.5 mg/kg), and PTX
(115 mg/kg) were injected intraperitoneally into C57BL/6J mice.
Taste tissues were collected at 24 and 48 h after drug injections.
To investigate effects of these drugs on taste progenitor cells, we
performed double immunostaining using antibodies against Ki67
and KCNQ1. Ki67 is a cell proliferation marker which can be used
to identify progenitor cells in the taste epithelium. KCNQ1, a
voltage-gated potassium channel protein, is a taste cell marker.
To investigate whether these drugs induce cell death in taste tissues,
we performed immunostaining using antibodies specific to
activated Caspase-3 or Caspase-6. Both caspases are executioner
caspases which, when activated, carryout proteolytic cleavage of
many proteins critical for cell survival. Our results show that all
three chemotherapy drugs significantly decreased the number of
Ki67-positive taste progenitor cells and increased the number of
apoptotic cells in the circumvallate epithelium. These results
suggest that taste progenitor cells and taste bud cells are
susceptible to the cytotoxic effects of chemotherapy drugs.
Acknowledgements: Supported by a grant from the Pennsylvania
Department of Health.
#P126
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
Endogenous Gustatory Response and Properties of
Immortalized Human Taste Cell Lines from
Lingual Epithelium
Andreas Hochheimer, Michael Krohn, Holger Zinke
B.R.A.I.N AG Zwingenberg, Germany
This abstract will be available at a later date.
Abstracts | 69
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