A genome-wide screen reveals a role for microRNA-1 in modulating cardiac cell polarity.
A genome-wide screen reveals a role for microRNA-1 in modulating cardiac cell polarity.
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DOI：
10.1016/j.devcel.2011.03.010
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发表时间：
2011-04-19
影响因子：
11.8
通讯作者：
Srivastava, Deepak
中科院分区：
文献类型：
--
作者：
King, Isabelle N.;Qian, Li;Liang, Jianping;Huang, Yu;Shieh, Joseph T. C.;Kwon, Chulan;Srivastava, Deepak
许多与心脏病有关的分子通路都起源于进化上古老的发育程序，这些程序严重依赖于基因剂量和时间。MicroRNA（miRNAs）在转录后调节基因剂量，其中，肌肉特异性miR-1对于体细胞/骨骼肌和心肌的发育和维持特别重要。为了确定由miR-1调控的途径，我们在果蝇中使用翅静脉图案作为生物测定进行了正向遗传筛选。我们发现了几个意想不到的基因，与dmiR-1的遗传相互作用，其中之一是kayak，编码发育调控转录因子。针对这种遗传关系的其他研究揭示了dmiR-1在调节心脏祖细胞极性方面的先前未被认识的功能。kay的哺乳动物直向同源物c-Fos在获得或丧失功能的miR-1突变小鼠的心脏中以应激依赖性方式失调。这些发现说明了基于果蝇的筛选在发现哺乳动物中miRNA和保守途径之间的交叉点方面的能力。
Many molecular pathways involved in heart disease have their roots in evolutionarily ancient developmental programs that depend critically on gene dosage and timing. MicroRNAs (miRNAs) modulate gene dosage post-transcriptionally, and among these, the muscle-specific miR-1 is particularly important for developing and maintaining somatic/skeletal and cardiac muscle. To identify pathways regulated by miR-1, we performed a forward genetic screen in Drosophila using wing-vein patterning as a biological assay. We identified several unexpected genes that genetically interacted with dmiR-1, one of which was kayak, encoding a developmentally-regulated transcription factor. Additional studies directed at this genetic relationship revealed a previously unappreciated function of dmiR-1 in regulating the polarity of cardiac progenitor cells. The mammalian orthologue of kay, c-Fos, was dysregulated in hearts of gain- or loss-of-function miR-1 mutant mice in a stress-dependent manner. These findings illustrate the power of Drosophila-based screens to find points of intersection between miRNAs and conserved pathways in mammals.
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DOI：
10.1073/pnas.85.2.339
发表时间：
1988-01-01
影响因子：
11.1
作者：
IZUMO, S;NADALGINARD, B;MAHDAVI, V
通讯作者：
MAHDAVI, V
DOI：
10.1073/pnas.0509535102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Kwon, C;Han, Z;Srivastava, D
通讯作者：
Srivastava, D
影响因子：
56.9
作者：
Bao, ZZ;Bruneau, BG;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
11.4
作者：
FRASCH, M;HOEY, T;LEVINE, M
通讯作者：
LEVINE, M
影响因子：
64.8
作者：
Fanto, M;Mlodzik, M
通讯作者：
Mlodzik, M