Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye
Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye
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DOI：
10.1038/17389
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发表时间：
1999-02-11
期刊：
影响因子：
64.8
通讯作者：
Mlodzik, M
中科院分区：
文献类型：
--
作者：
Fanto, M;Mlodzik, M
平面极性见于整个动物界的表皮衍生结构（1，2）。在果蝇的眼睛中，平面极性反映在小眼（眼睛单位）在背腹中线或赤道上的镜像对称排列中;赤道背侧和腹侧的小眼表现出相反的手性（3-5）。光感受器R3和R4在小眼极性的建立中是必不可少的（6-11）。R3细胞被认为通过受体Frizzled（Fz）接收极化信号，在R4细胞之前或更高水平，在相邻的R3和R4细胞之间产生差异（6，7，9，10）。R3/R4对中Fz的功能丧失和过表达均导致极性缺陷和镜像对称性丧失（6、7、9、10、12）。在这里，我们确定Notch和三角洲（DI）作为显性增强子的表型所产生的过表达的FZ和凌乱（dsh），它编码的信号传导组件下游的FZ，我们表明，DI介导的激活Notch是必需的小眼极性的建立。而fz信号需要指定R3，Notch信号诱导R4的命运。我们的数据表明，Dl是R3中Fz/Dsh信号传导的转录靶标，并激活相邻R4前体中的Notch。这种双层机制解释了Fz激活水平和/或时间的微小差异如何可靠地产生二元细胞命运决定，从而导致R3和R4以及小眼手性的规范。
Planar polarity is seen in epidermally derived structures throughout the animal kingdom(1,2). In the Drosophila eye, planar polarity is reflected in the mirror-symmetric arrangement of ommatidia (eye units) across the dorsoventral midline or equator; ommatidia on the dorsal and ventral sides of the equator exhibit opposite chirality(3-5). Photoreceptors R3 and R4 are essential in the establishment of the polarity of ommatidia(6-11). The R3 cell is thought to receive the polarizing signal, through the receptor Frizzled (Fz), before or at higher levels then the R4 cell, generating a difference between neighbouring R3 and R4 cells(6,7,9,10). Both loss-of-function and overexpression of Fz in the R3/R4 pair result in polarity defects and loss of mirror-image symmetry(6,7,9,10,12). Here we identify Notch and Delta (Dl) as dominant enhancers of the phenotypes produced by overexpression of fz and dishevelled (dsh), which encodes a signalling component downstream of Fz, and we show that Dl-mediated activation of Notch is required for establishment of ommatidial polarity. Whereas fz signalling is required to specify R3, Notch signalling induces the R4 fate. Our data indicate that Dl is a transcriptional target of Fz/Dsh signalling in R3, and activates Notch in the neighbouring R4 precursor. This two-tiered mechanism explains how small differences in the level and/or timing of Fz activation reliably generate a binary cell-fate decision, leading to specification of R3 and R4 and ommatidial chirality.