Domínguez M, Wasserman J D, Freeman M
MRC Laboratory of Molecular Biology, Cambridge, UK.
Curr Biol. 1998 Sep 24;8(19):1039-48. doi: 10.1016/s0960-9822(98)70441-5.
During animal development, cells need to make spatially and temporally regulated fate decisions. These decisions are largely controlled by intercellular signalling, often through receptor tyrosine kinases. One of these, the epidermal growth factor receptor (EGFR), regulates multiple cell fate decisions. Its importance in the recruitment of photoreceptors in the developing fly eye, a useful model for neural development, has already been reported. Other EGFR functions in the eye have not been characterised.
We have examined the consequences of removing or activating the EGFR at different stages of eye development. The earliest stages of assembly occurred normally within EGFR- clones--the morphogenetic furrow was unimpeded and the R8 photoreceptor was specified. All subsequent photoreceptor recruitment was blocked. EGFR- clones had a characteristic shape indicating that they had undergone substantial cell death posterior to the furrow, where the differentiation program is normally activated; consistent with this, excess apoptosis was detected. We found that the receptor also regulates cell proliferation in the disc, has an early function at the disc margin (where the morphogenetic furrow initiates) and contributes to the regulation of spacing of the R8 precursors. Finally, we found that activation of the receptor is sufficient to trigger non-R8 photoreceptor development, even in cells in front of the furrow or in the absence of the proneural gene atonal.
At least five distinct functions of EGFR signalling need to be integrated during fly eye development. These include roles in cell proliferation, survival and differentiation.
在动物发育过程中，细胞需要做出空间和时间上受到调控的命运决定。这些决定很大程度上受细胞间信号传导控制，通常是通过受体酪氨酸激酶。其中之一，表皮生长因子受体（EGFR），调控多种细胞命运决定。其在发育中的果蝇眼睛（神经发育的一个有用模型）中对光感受器募集的重要性已有报道。EGFR在眼睛中的其他功能尚未得到表征。
我们研究了在眼睛发育的不同阶段去除或激活EGFR的后果。组装的最早阶段在EGFR克隆中正常发生——形态发生沟不受阻碍，R8光感受器得以确定。所有后续的光感受器募集均被阻断。EGFR克隆具有特征性形状，表明它们在沟后方经历了大量细胞死亡，而在正常情况下，分化程序正是在那里被激活；与此一致的是，检测到了过量的细胞凋亡。我们发现该受体还调控盘中的细胞增殖，在盘边缘（形态发生沟起始处）具有早期功能，并有助于调节R8前体细胞的间距。最后，我们发现受体的激活足以触发非R8光感受器发育，即使是在沟前方的细胞中或在缺乏神经前体基因无调性的情况下。
在果蝇眼睛发育过程中，EGFR信号传导的至少五种不同功能需要整合。这些功能包括在细胞增殖及存活和分化中的作用。
