MOLECULAR BASIS OF DEVELOPMENTAL CELL INTERACTIONS

尽管在操纵分泌型的基因方面取得了巨大的进展， 信号分子，分泌型形态发生素与接触依赖型 在驱动模式化和极性信号的相互作用中， 路径仍然不清楚。此外，很少有好的候选分子， 可能介导推定的接触依赖性信号传导。 这些是理解模式形成的关键问题， 观察到“细胞在发育过程中 通过组织增长和变化， 根据位置信息的发育命运， 并通过与邻居的互动来解释”（Wolpert，1969）。 在细胞内起作用的基因克隆，如disevelled和shaggy 和下游的分泌分子，如无翅可以组织异位 以特定的方式定位。最简单的解释是， 这些观察结果表明，局部细胞相互作用驱动了模式化 当克隆被诱导时。然而，刺激调控生长的克隆 也可以导致分泌分子的异位激活， 或是十肢瘫痪我们进一步发现wg的信号传导抑制了 dpp的表达，反之亦然。因此，为了解决分泌的作用， 与接触依赖的相互作用，它是必要的，以分离 分泌分子的作用与接触介导的 交互.在这里，我们提出的实验正是这样做的。的 dsh和sgg克隆组织模式的潜力，当克隆 细胞或邻近细胞无法产生或响应 将确定推定的形态发生剂DPP和WG;因此，分离 由于接触依赖机制的影响，从那些由于扩散 信号.这种克隆刺激生长的潜力不依赖于 还将直接评估最终规格。脂肪基因将会 测试以确定脂肪是否是介导接触的候选者- 依赖信号继续研究以阐明结构基础 DSH在传输基于继电器的极性信号与 将传导分泌的WG信号。dsh，sgg， 脂肪活性对连接相关的亚细胞定位的影响 蛋白质和细胞亲和力也将被检查，以测试 假设组织结构涉及不同位置 特异性细胞亲和性。

Despite dramatic advances in the manipulation of genes for secreted signaling molecules, the role of secreted morphogens vs. contact-dependent interactions in driving both the patterning and polarity signaling pathways remains unclear. Further, very few good candidate molecules that might mediate putative contact-dependent signaling have been described. These are key issues for understanding pattern formation and they address the mechanistic basis of the observation that "cells in a developmental field respond to changes in position by organizing growth and changes in developmental fate according to positional information which is derived and interpreted via interactions with their neighbors" (Wolpert, 1969). Clones of genes such as dishevelled and shaggy that act intracellularly and downstream of secreted molecules such as wingless can organize ectopic pattern in a position specific manner. In the simplest interpretation, these observations suggest that local cell interactions drive patterning when clones are induced. However, clones which stimulate regulatory growth can also lead to ectopic activation of secreted molecules such as wingless or decapentaplegic. We have further found that signaling by wg suppresses expression of dpp and visa versa. Thus, to address the role of secreted morphogens vs. contact-dependent interactions, it is essential to separate the effects of secreted molecules from those of contact-mediated interactions. Here we propose experiments to do exactly that. The potential of dsh and sgg clones to organize pattern when either the clonal cells or neighboring cells are unable to produce or respond to the putative morphogens dpp and wg will be determined; thus, isolating the effects due to contact-dependent mechanisms from those due to diffusible signals. The potential of such clones to stimulate growth independent of fate specification will also be directly assessed. The fat gene will be tested to determine whether fat is a candidate for mediating in contact- dependent signaling. Continuing studies to elucidate the structural basis of DSH's role in transmitting a relay based polarity signal vs the secreted wg signal will be conducted. The effect of loss of dsh, sgg and fat activity on the subcellular localization of junction associated proteins and on cell affinities will also be examined to test the hypothesis that tissue organization involves differential position specific cell affinity.