Epithelial Cell Proliferation and Apoptosis in the Developing Murine Palatal Rugae

Takanosu, Masamine; Amasaki, Hajime; Iwama, Yoshie; Ogawa, Miyuki; Hibi, Shunya; Suzuki, Kaori

doi:10.1046/j.1439-0264.2002.00351.x

Cited by 9 publications

(16 citation statements)

References 23 publications

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“…Spatial and temporal changes of cell proliferation, especially between the placode and interplacode areas, are closely related to the development of the chick scale [22,23]. In our previous study based on the distribution of cells incorporating BrdU and on TUNEL analysis, it was suggested that spatial and temporal variations in cell proliferation and/or apoptosis of the epithelium were intimately involved with murine PR formation [20]. Apoptosis plays an important role in controlling cell populations during human embryogenesis [16].…”

Section: Discussionmentioning

confidence: 99%

“…Each edge of PR is orientated aborally, according to our previous scanning electron microscopical and gross anatomical examinations [20]. Murine PR develop through two steps; the first step being the formation of the epithelial placode (EP), and the second protrusion and growth in the aboral direction.…”

Section: Discussionmentioning

confidence: 99%

“…PR patterns form quite regular structures. We have studied PR pattern formation mechanisms [1,2,20,21]. PR develop similarly to other organs in the epithelium, eg., hair follicles [7,8], and feather buds [7,9].…”

mentioning

confidence: 99%

“…Palatine rugae (PR) are formed as a corrugated pattern on the hard plate of the murine oral roof [1,2,4,20,21]. PR patterns form quite regular structures.…”

mentioning

confidence: 99%

“…Pattern formation of PR could also involve spatiotemporally regulated epithelial cell proliferation and apoptotic death, as occurs with chick feather [9] and scale [22,23] development. Our previous study indicated that differential cell apoptosis during placode formation might maintain the epithelial population in the PR rudiment [20]. Apoptosis may regulate cell population and play a role in organogenesis [5,14,18].…”

mentioning

confidence: 99%

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Distribution of Apoptotic Cells and Apoptosis-Related Molecules in the Developing Murine Palatine Rugae.

Amasaki

Ogawa

Nagasao

et al. 2002

The Journal of Veterinary Medical Science

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ABSTRACT. Distribution of apoptotic cells and expression of the apoptosis-related factors p53, bcl-2 and bad during morphogenesis of the murine palatine rugae (PR) were examined histochemically using the terminal deoxynucleotidyl transferase-mediated UTP nick endlabeling (TUNEL) technique and specific antibodies against apoptosis and cell cycle-related molecules. Formation of the PR rudiment was controlled by cell proliferation and apoptosis in the palatal epithelium. TUNEL-positive cells were detected only at the epithelial placode area at 12.5-13.5 days post coitus (dpc), but only a few cells were positive at the protruding PR area at 14.5-16.5 dpc. Bcl-2 protein was expressed mainly in the areas outside of those containing TUNEL-positive cells at 15.5 -6.5 dpc. P53 protein was not detected throughout gestation. Bad was detected in the epithelial layer at 13.5 and 15.5 dpc and overlapping the apoptotic area at 13.5-15.5 dpc. Apoptosis of palatal epithelial cells might therefore involve spatiotemporally regulated expression of bad during murine PR development. KEY WORDS: apoptosis, bad, bcl2, morphogenesis, palatal ridge.J. Vet. Med. Sci. 64(12): 1103-1106 Palatine rugae (PR) are formed as a corrugated pattern on the hard plate of the murine oral roof [1,2,4,20,21]. PR patterns form quite regular structures. We have studied PR pattern formation mechanisms [1,2,20,21]. PR develop similarly to other organs in the epithelium, eg., hair follicles [7,8], and feather buds [7,9]. Epithelium and subepithelial mesenchyme of the epithelial organs develop under the reciprocal controls of each different tissue. Pattern formation of PR could also involve spatiotemporally regulated epithelial cell proliferation and apoptotic death, as occurs with chick feather [9] and scale [22,23] development. Our previous study indicated that differential cell apoptosis during placode formation might maintain the epithelial population in the PR rudiment [20]. Apoptosis may regulate cell population and play a role in organogenesis [5,14,18]. Apoptosis can be induced by growth factor withdrawal, glucocorticoids [13,26], fas ligand/fas interaction [12,19], killer T cells [17], ionising radiation, drugs, oxygen radicals [3], tumour necrosis factor α (TNFα) TNF-receptor 1 interaction [15] etc. However, the signals inducing epithelial cell apoptosis at the PR epithelial placode are not known.In the present study, we examined the spatiotemporal distribution of apoptotic cells by using the terminal deoxynucleotidyl transferase-mediated UTP nick end-labeling (TUNEL) technique and assessing the presence of p53 (antitumor apoptosis enhancement factor) [10], bcl-2 (B cell lymphoma/leukaemia-2) [24], bad (apoptosis enhancement factor) [25] molecules by immunochemistry during PR formation in the mouse. MATERIALS AND METHODSAnimals: All animals were kept in an air-conditioned room, and fed standard laboratory food pellets and water ad libitum. Pro-estrous female mice were mated with male mice overnight. Gestation was confirmed by the presence of a vagina...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Palatine rugae (PR) are formed as a corrugated pattern on the hard plate of the murine oral roof [1,2,4,20,21]. PR patterns form quite regular structures.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Distribution of Apoptotic Cells and Apoptosis-Related Molecules in the Developing Murine Palatine Rugae.

Amasaki

Ogawa

Nagasao

et al. 2002

The Journal of Veterinary Medical Science

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Importance of region-specific epithelial rearrangements in mouse rugae development

et al. 2011

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Epithelial appendages on palatal rugae develop during mouse palatogenesis through epithelial thickening and pattern formation. Recently, the patterned formation of nine rugae was observed together with the specific expression patterns of Shh in rodents. However, no crucial evidence was found for a direct association between Shh expression and the distinct structural formation of rugae. In order to reveal possible relationships, we investigated the morphological changes of rugae and expression patterns of Shh directly by in vitro organ culture at embryonic day 13 (E13) for 2 days. To compare and examine the diverse growing aspects of the palate and rugae, we carefully observed the detailed morphogenesis, with cell proliferation of the rugae occurring between E13 and E14.5. After 2 days of cultivation at E13, DiI micro-injections revealed that the middle part of the palate, adjacent to the upper molar-forming region, contributed to the formation of the subsequent structure of rugae by extensive cell rearrangement and proliferation within the epithelium in the preferred anteroposterior direction. The results also defined the intimate relationship between Shh expression and rugae formation.

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Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1, a preferential small molecule activator of procaspase-3, in healthy dogs

et al. 2010

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PAC-1 is a preferential small molecule activator of procaspase-3 and has potential to become a novel and effective anticancer agent. The rational development of PAC-1 for translational oncologic applications would be advanced by coupling relevant in vitro cytotoxicity studies with pharmacokinetic investigations conducted in large mammalian models possessing similar metabolism and physiology as people. In the present study, we investigated whether concentrations and exposure durations of PAC-1 that induce cytotoxicity in lymphoma cell lines in vitro can be achievable in healthy dogs through a constant rate infusion (CRI) intravenous delivery strategy. Time- and dose-dependent procaspase-3 activation by PAC-1 with subsequent cytotoxicity was determined in a panel of B-cell lymphoma cells in vitro. The pharmacokinetics of PAC-1 administered orally or intravenously was studied in 6 healthy dogs using a crossover design. The feasibility of maintaining steady state plasma concentration of PAC-1 for 24 or 48 hours that paralleled in vitro cytotoxic concentrations was investigated in 4 healthy dogs. In vitro, PAC-1 induced apoptosis in lymphoma cell lines in a time- and dose-dependent manner. The oral bioavailability of PAC-1 was relatively low and highly variable (17.8 ± 9.5%). The achievement and maintenance of predicted PAC-1 cytotoxic concentrations in normal dogs was safely attained via intravenous CRI lasting for 24 or 48 hours in duration. Using the dog as a large mammalian model, PAC-1 can be safely administered as an intravenous CRI while achieving predicted in vitro cytotoxic concentrations.

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Epithelial Cell Proliferation and Apoptosis in the Developing Murine Palatal Rugae

Cited by 9 publications

References 23 publications

Distribution of Apoptotic Cells and Apoptosis-Related Molecules in the Developing Murine Palatine Rugae.

Distribution of Apoptotic Cells and Apoptosis-Related Molecules in the Developing Murine Palatine Rugae.

Importance of region-specific epithelial rearrangements in mouse rugae development

Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1, a preferential small molecule activator of procaspase-3, in healthy dogs

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