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阿糖胞苷对细胞增殖的抑制作用及其对鸡视网膜空间和时间分化模式的干扰。

Inhibition of cell proliferation by cytosine-arabinoside and its interference with spatial and temporal differentiation patterns in the chick retina.

作者信息

Liu L, Halfter W, Layer P G

出版信息

Cell Tissue Res. 1986;244(3):501-13. doi: 10.1007/BF00212527.

DOI:10.1007/BF00212527
PMID:3719673
Abstract

Incubation of chick embryos with 200 nmoles/egg of cytosine arabinoside (AraC) completely inhibits cell proliferation in the embryo. At an age older than embryonic day 4 (E4) more than 90% of the embryos survive this treatment. The drug induces various malformations; in particular the retina is heavily affected. This simple method offers the possibility to study the effect of a more or less decreased cell production on processes of further differentiation and histogenesis of retinal tissue. The following results are obtained: In spite of the inhibition of cell proliferation in the retina by AraC an abnormally thick basal lamina is found and the expansion of the eye still proceeds, indicating that eye growth is not only dependent on retinal cell numbers. Stereotyped malformations of retinal histogenesis are induced and categorized into three groups: in addition to areas of normal structure cells are found arranged in rosettes and in half-rosettes sometimes linked by areas of undefined transient cell arrangements. The results point to a strong tendency of a severely diminished cell population to form regularly laminated retinal-like structures as long as a minimal ratio of cell types is given. The spatio-temporal appearance of the type of retinal malformation in a given retinal area is dependent on the time of AraC exposure and thus on the degree of differentiation reached at a "spatio-temporal spot": Full rosettes develop at earlier, and half-rosettes at later stages of AraC interference. Furthermore, deformities first appear on temporal and ventral sides. Thus, the establishment of these malformations follows and reflects the normal sequence of differentiation within the retina. Cells within rosettes organize in specific layers and start to differentiate normally. This shows that earlier formed cells are not dependent on the influence of factors derived from cells that are formed later for their proper differentiation.

摘要

用200纳摩尔/枚鸟嘌呤阿拉伯糖苷(AraC)孵育鸡胚,可完全抑制胚胎中的细胞增殖。在胚胎第4天(E4)之后的年龄阶段,超过90%的胚胎能在这种处理下存活。该药物会诱发各种畸形;特别是视网膜受到严重影响。这种简单方法为研究细胞产生或多或少减少对视网膜组织进一步分化和组织发生过程的影响提供了可能性。得到了以下结果:尽管AraC抑制了视网膜中的细胞增殖,但仍发现基底膜异常增厚,且眼睛仍在继续扩张,这表明眼睛的生长不仅取决于视网膜细胞数量。诱发了视网膜组织发生的刻板畸形并将其分为三组:除了正常结构区域外,还发现细胞呈玫瑰花结状和半玫瑰花结状排列,有时由未定义的瞬时细胞排列区域相连。结果表明,只要细胞类型的比例最小,细胞数量严重减少的情况下仍有强烈的形成规则分层视网膜样结构的趋势。给定视网膜区域中视网膜畸形类型的时空出现取决于AraC暴露的时间,因此取决于在“时空点”达到的分化程度:完整的玫瑰花结在AraC干扰的早期形成,半玫瑰花结在后期形成。此外,畸形首先出现在颞侧和腹侧。因此,这些畸形的形成遵循并反映了视网膜内正常的分化顺序。玫瑰花结内的细胞组织成特定层并开始正常分化。这表明早期形成的细胞在其正常分化过程中不依赖于后期形成的细胞衍生因子的影响。

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