The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction.
The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction.
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DOI：
10.1126/scisignal.2002437
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发表时间：
2012-06-12
影响因子：
7.3
通讯作者：
Chang C
中科院分区：
文献类型：
--
作者：
Zou Y;Chiu H;Domenger D;Chuang CF;Chang C
lin-4 (miR-125) microRNAs are deeply conserved across animal phylogeny. They are among the first microRNAs discovered and were implicated in regulating developmental timing in C. elegans. In this study, we report that mutations in lin-4 microRNA specifically suppress the AVM axon guidance defects in slt-1 mutants through enhancement of netrin attraction. lin-4 expression in AVM neurons rescued lin-4 mutant phenotypes in AVM axon guidance, suggesting that lin-4 acts cell autonomously in AVM to inhibit its axon attraction to netrin. lin-4 is expressed strongly in the AVM neuron when its axon guidance is underway, and is almost undetectable in the ALM neuron whose axon guidance is netrin independent. The transcription factor lin-14, a necessary target of lin-4 microRNA in the AVM neurons, stimulates netrin-mediated AVM axon ventral guidance. lin-14’s positive effect in netrin attraction is mediated by the receptor unc-40 (DCC) and its cofactor madd-2 functioning through a combination of the unc-34 (Ena) and ced-10 (Rac1)-dependent downstream pathways. lin-14 stimulates netrin-mediated axon attraction in part by enhancing UNC-40 protein expression. Our study indicates that the eventual down-regulation of lin-14 activity in the AVM neurons at the end of axon guidance is caused by lin-4 microRNA inhibition.
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影响因子：
9.2
作者：
Quinn, Christopher C.;Pfeil, Douglas S.;Wadsworth, William G.
通讯作者：
Wadsworth, William G.
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
2.5
作者：
Olsson-Carter, Katherine;Slack, Frank J.
通讯作者：
Slack, Frank J.
影响因子：
56.9
作者：
Chang, C;Yu, TW;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
11.8
作者：
Lin, SY;Johnson, SM;Slack, FJ
通讯作者：
Slack, FJ