Bryant P J, Schmidt O
Developmental Biology Center, University of California, Irvine 92717.
J Cell Sci Suppl. 1990;13:169-89. doi: 10.1242/jcs.1990.supplement_13.16.
The imaginal discs of Drosophila provide a favorable system for the analysis of the mechanisms controlling developmental cell proliferation, because of the separation in time between cell proliferation and differentiation, and the facility with which controlling genes can be identified and characterized. Imaginal discs are established in the embryo, and grow by cell proliferation throughout the larval period. Proliferation terminates in a regular spatial pattern during the final stages of larval development and the first day of pupal development. Cell proliferation can be locally reactivated in growth-terminated imaginal discs by removing part of the disc and culturing the remaining fragment in an adult host. The pattern of proliferation in these fragments suggests that cell proliferation in imaginal discs is controlled by direct interactions between cells and their neighbors. Proliferation appears to be stimulated by positional information differences, and these differences are reduced by the addition of new cells during tissue growth. Genes involved in cell proliferation control have been identified by collecting and analyzing recessive lethal mutations which cause overgrowth of imaginal discs. In some of these mutants (fat, lgd, c43, dco) the overgrowing tissue is hyperplastic; it retains its single-layered epithelial structure and is capable of differentiating. In two of the hyperplastic mutants (dco and c43), the imaginal discs show a failure of gap-junctional cell communication, suggesting that this form of cell communication may be involved in termination of proliferation. In other mutants the overgrowing disc tissue is neoplastic: it loses its structure and ability to differentiate, becoming a tumorous growth. The two genes that give a neoplastic phenotype (dlg and lgl) have been cloned and cDNAs of one of them (lgl) sequenced. The lgl gene encodes a cell surface molecule with significant homology to calcium-dependent cell adhesion molecules (cadherins). The expression of lgl at the time of termination of cell proliferation suggests that there are changes in the way that cells interact with one another at these times, and that these changes may be implemented by cell adhesion molecules. Direct cell contact within the epithelium, as well as signalling through gap junctions, appears to be involved in the cell interactions needed for the termination of cell proliferation. Mutations in genes encoding the Drosophila homologs of growth factors, growth factor receptors and oncogenes usually show an effect on cell-fate decisions rather than cell proliferation control, but this may be because oncogenic mutations in these genes would be dominant lethals and would therefore not be identified by conventional genetic analysis.
果蝇的成虫盘为分析控制发育中细胞增殖的机制提供了一个有利的系统，这是因为细胞增殖和分化在时间上是分开的，而且易于鉴定和表征调控基因。成虫盘在胚胎中形成，并在整个幼虫期通过细胞增殖生长。在幼虫发育的最后阶段和蛹发育的第一天，增殖以规则的空间模式终止。通过切除成虫盘的一部分并将剩余片段在成年宿主体内培养，可以在生长终止的成虫盘中局部重新激活细胞增殖。这些片段中的增殖模式表明，成虫盘中的细胞增殖是由细胞与其邻居之间的直接相互作用控制的。增殖似乎受到位置信息差异的刺激，而这些差异在组织生长过程中由于新细胞的添加而减小。通过收集和分析导致成虫盘过度生长的隐性致死突变，已经鉴定出参与细胞增殖控制的基因。在其中一些突变体（fat、lgd、c43、dco）中，过度生长的组织是增生性的；它保留其单层上皮结构并且能够分化。在两个增生性突变体（dco和c43）中，成虫盘显示间隙连接细胞通讯失败，这表明这种细胞通讯形式可能参与增殖的终止。在其他突变体中，过度生长的盘组织是肿瘤性的：它失去其结构和分化能力，变成肿瘤性生长。产生肿瘤表型的两个基因（dlg和lgl）已被克隆，其中一个（lgl）的cDNA已被测序。lgl基因编码一种与钙依赖性细胞粘附分子（钙粘蛋白）具有显著同源性的细胞表面分子。lgl在细胞增殖终止时的表达表明，在这些时候细胞相互作用的方式发生了变化，并且这些变化可能由细胞粘附分子实现。上皮内的直接细胞接触以及通过间隙连接的信号传导，似乎参与了细胞增殖终止所需的细胞相互作用。编码果蝇生长因子、生长因子受体和癌基因同源物的基因中的突变通常对细胞命运决定而不是细胞增殖控制有影响，但这可能是因为这些基因中的致癌突变将是显性致死的，因此不会通过传统的遗传分析被鉴定出来。
