The role of RhoA in tissue polarity and Frizzled signalling

The role of RhoA in tissue polarity and Frizzled signalling
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DOI:
10.1038/387292a0
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发表时间:
1997-05-15
期刊:
影响因子:
64.8
通讯作者:
Mlodzik, M
Mlodzik, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Strutt, DI;Weber, U;Mlodzik, M

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果蝇的组织极性基因是在表皮结构(1,2)中正确建立平面极性所必需的,这在眼睛中表现为小眼相对于背腹中线的镜像对称排列。卷曲(Fz)、蓬乱(Dsh)和多刺腿(pk-sple)基因的突变导致了这种镜像对称性的丧失(3-5)。FZ编码一种蛇形受体样的跨膜蛋白,是接收和发送极性信号所必需的(5,6),除了Dsh作用于FZ(7)下游外,人们对所涉及的信号通路(S)知之甚少。我们已经在果蝇RhoA p21GTPase的同源物中发现了突变,通过对它们的表型分析表明,RhoA是产生组织极性所必需的,遗传相互作用表明RhoA在FZ和Dsh介导的信号转导中发挥了作用,并进一步表明JNK/SAPK样激酶参与其中,这些数据与类似于酵母信息素信号通路的FZ/RhoA信号级联一致(8),并被提议激活脊椎动物细胞中的血清反应因子(SRF)(9)。
The tissue polarity genes of Drosophila are required for correct establishment of planar polarity in epidermal structures(1,2), which in the eye is shown in the mirror-image symmetric arrangement of ommatidia relative to the dorsoventral midline. Mutations in the genes frizzled (fz), dishevelled (dsh) and prickle-spiny-legs (pk-sple) result in the loss of this mirror-image symmetry(3-5). fz encodes a serpentine receptor-like transmembrane protein required for reception and transmission of a polarity signal(5,6), Little else is known of the signalling pathway(s) involved other than that Dsh acts downstream of Fz(7). We have identified mutations in the Drosophila homologue of RhoA p21 GTPase, and by analysis of their phenotype show that RhoA is required for the generation of tissue polarity, Genetic interactions indicate a role for RhoA in signalling mediated by Fz and Dsh, and furthermore suggest that JNK/SAPK-like kinases are involved, These data are consistent with a Fz/RhoA signalling cascade analogous to the yeast pheromone signalling pathway(8) and that proposed for activation of the serum response factor (SRF) in vertebrate cells(9).