Circadian influence on the frequency of labeled mitoses method in the stratified squamous epithelium of the mouse esophagus and tongue

Burns, E. Robert; Scheving, Lawrence E.; Fawcett, D F; Gibbs, W M; Galatzan, R E

doi:10.1002/ar.1091840302

Cited by 40 publications

(21 citation statements)

References 11 publications

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“…injected BrdU in the mouse is 2–3 hours [22]. In mouse lingual epithelium, the duration of S-phase is ≈5 h while G2+ half of M phase is estimated at 4.2 h [23]. Assuming that EdU has similar dynamics to BrdU, very few labeled cells detected 4 h after injection should have already completed mitosis.…”

Section: Resultsmentioning

confidence: 99%

“…Although Sullivan et al [33] had a much smaller sample size than ours, their reported incidence of labeled cells within the boundaries of taste buds, based on confocal imaging, is remarkably similar to ours (Figure 3F). Because the duration of S and (G2+ ½M) phases in mouse lingual epithelium were estimated at 5.3 h and 4.2 h respectively [23], it appears unlikely that cells could have incorporated detectable levels of EdU and completed mitosis within 4 h, our shortest post-injection interval. Thus, we suggest that a small fraction (≤10%) of taste cells may be born inside taste buds, while the very large majority migrate in from the surrounding epithelium.…”

Section: Discussionmentioning

confidence: 99%

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Functional Cell Types in Taste Buds Have Distinct Longevities

2013

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Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8–12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2′-deoxyuridine (EdU) to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor) taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic) taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional Cell Types in Taste Buds Have Distinct Longevities

2013

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“…Of the numerous prior studies in the mouse (Brown & Berry 1968; Izquierdo & Gibbs 1972; Moller & Larsen 1978), and the hamster (Burns et al. 1975; Hume & Potten 1976; Dörr & Kummermehr 1991; Dörr et al.…”

Section: Discussionmentioning

confidence: 99%

Cell kinetic studies in the murine ventral tongue epithelium: thymidine metabolism studies and circadian rhythm determination

et al. 2002

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The oral mucosa is a rapidly replacing body tissue that has received relatively little attention in terms of defining its cell kinetics and cellular organization. The tissue is sensitive to the effects of cytotoxic agents, the consequence of which can be stem cell death with the subsequent development of ulcers and the symptoms of oral mucositis. There is considerable interest in designing strategies to protect oral stem cells and, hence, reduce the mucositis side-effects in cancer therapy patients. Here we present details of a new histometric approach designed to investigate the changing patterns in cellularity in the ventral tongue mucosa. This initial paper in a series of four papers presents observations on the changing patterns in the labelling index following tritiated thymidine administration, which suggest a delayed uptake of tritiated thymidine from a long-term intracellular thymidine pool, a phenomenon that will complicate cell kinetic interpretations in a variety of experimental situations. We also provide data on the changing pattern of mitotic activity through a 24-h period (circadian rhythms). Using vincristine-induced stathmokinesis, the data indicate that 54% of the basal cells divide each day and that there is a high degree of synchrony in mitotic activity with a mitotic peak occurring around 13.00 h. The mitotic circadian peak occurs 9-12 h after the circadian peak in DNA synthesis. The data presented here and in the subsequent papers could be interpreted to indicate that basal cells of BDF1 mice have an average turnover time of about 26-44 h with some cells cycling once a day and others with a 2- or 3-day cell cycle time.

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“…Sprague-Dawley male rats (weighing about 250 g, n=6) were killed by a lethal injection of sodium pentothal. Animals were always sacrificed in the early morning, to ensure standard parameters with respect to the circadian rhythm of the mitotic index of the digestive tract epithelia, the peak occurring during the first half of the diurnal phase [1] . Human material (n = 6 for each organ) was obtained from healthy margins of surgical specimens.…”

Section: Methodsmentioning

confidence: 99%