Seddon S V, Walker D M, Williams D, Williams E D
Department of Oral Surgery Medicine and Pathology, Dental School, University of Wales College of Medicine, Cardiff, UK.
Cell Prolif. 1992 Mar;25(2):115-24. doi: 10.1111/j.1365-2184.1992.tb01485.x.
Knowledge of the kinetics and stem cell localization of the mouse lingual epithelium is largely based on studies using DNA labelling techniques. We have adopted a different approach, using histochemistry for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). We have deduced clone size and morphology from studies of patch size and distribution in mice heterozygous for G6PD deficiency and from the identification of clonal enzyme loss induced in normal mice by application of a mutagen. Lingual epithelium of female mice (CBA X GPDX) heterozygous for G6PD deficiency showed multiple clearly defined patches of strong or weak enzyme activity, corresponding in intensity to the strong staining uniformly present in the normal parental strain (CBA) or to the weak staining uniformly present in the G6PD deficient parental strain (GPDX). This pattern results from the random suppression of either the paternal or the maternal X chromosome in each cell early in embryonic development, and the subsequent inheritance of X inactivation in daughter cells, giving rise to phenotypic patches each composed of one or more clones. The patch borders intersected the base of the lingual epithelium at small indentations or at the apices of connective tissue papillae; the surface intersection in some cases bisected filiform papillae. Patch width measured in tissue sections at the mid rete ridge level, showed a clear mode close to 40 microns, corresponding very closely to the mode for rete ridge width (i.e. distance between connective tissue papillae). Further evidence for clonal organization was obtained by inducing mutations in the lingual epithelium of CBA mice by topical mutagen application. A few clearly defined patches of enzyme loss were found with a mean diameter of 36 microns. Their morphology was very similar to that of patches in the heterozygous animals. We interpret these patches as clones derived from stem cells with induced somatic G6PD mutations. We conclude that the mouse lingual epithelium is a stem cell epithelium composed of clonal units of about 40 microns diameter, based on the rete ridge structure and that both connective tissue papillae and filiform papillae occur at the junction of two or more epithelial clones.
小鼠舌上皮的动力学和干细胞定位知识主要基于使用DNA标记技术的研究。我们采用了一种不同的方法，即利用组织化学检测X连锁酶葡萄糖-6-磷酸脱氢酶（G6PD）。我们通过研究G6PD缺乏杂合小鼠的斑块大小和分布，以及通过应用诱变剂诱导正常小鼠产生的克隆性酶缺失，推断出克隆大小和形态。G6PD缺乏杂合的雌性小鼠（CBA×GPDX）的舌上皮显示出多个清晰界定的强或弱酶活性斑块，其强度分别对应于正常亲本品系（CBA）中均匀存在的强染色或G6PD缺乏亲本品系（GPDX）中均匀存在的弱染色。这种模式是由于在胚胎发育早期每个细胞中父本或母本X染色体的随机抑制，以及随后子细胞中X染色体失活的遗传，从而产生了每个由一个或多个克隆组成的表型斑块。斑块边界在小凹陷处或结缔组织乳头顶端与舌上皮基部相交；在某些情况下，表面相交将丝状乳头一分为二。在网嵴中部水平的组织切片中测量的斑块宽度显示，一个明显的众数接近40微米，与网嵴宽度（即结缔组织乳头之间的距离）的众数非常接近。通过在CBA小鼠的舌上皮局部应用诱变剂诱导突变，获得了克隆组织的进一步证据。发现了一些清晰界定的酶缺失斑块，平均直径为36微米。它们的形态与杂合动物中的斑块非常相似。我们将这些斑块解释为源自具有诱导体细胞G6PD突变的干细胞的克隆。我们得出结论，基于网嵴结构，小鼠舌上皮是一种由直径约40微米的克隆单位组成的干细胞上皮，并且结缔组织乳头和丝状乳头都出现在两个或更多上皮克隆的交界处。
