miR-9a prevents apoptosis during wing development by repressing Drosophila LIM-only.

miR-9a prevents apoptosis during wing development by repressing Drosophila LIM-only.
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miR-9a通过抑制果蝇lim抑制果蝇在机翼发育过程中的细胞凋亡。

DOI:
10.1016/j.ydbio.2009.11.025
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发表时间:
2010-02-01
影响因子:
2.7
通讯作者:
Lai, Eric C.
Lai, Eric C.
中科院分区:
生物学3区
文献类型:
--
作者:
Bejarano, Fernando;Smibert, Peter;Lai, Eric C.

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果蝇mir-9a的损失引起感觉刚毛的微妙增加,但翅膀组织的实质性损失。在这里,我们建立了后者的表型主要是由于异位凋亡的背翅原基,我们可以拯救翅膀的发展,在没有这种microRNA的背特异性抑制凋亡。这种细胞凋亡是去抑制果蝇LIM(dLMO)的结果,它编码翅膀和神经发育的转录调节因子。我们观察到内源性dLMO和GFP-dLMO 3'UTR传感器在mir-9a突变体翼克隆中的细胞自主升高,并且dLMO的杂合性挽救了mir-9a突变体的凋亡和翼缺陷。我们还提供了证据表明,dLMO,除了无意义的,有助于刚毛缺陷的mir-9a突变体。出乎意料的是,在mir-9a突变克隆中观察到的dLMO上调、Cut缺失和成虫翅缘缺陷并没有被miRNA生物合成因子Dicer-1或Pasha的克隆缺失所重现,即使这些突变条件类似地去抑制miR-9a和dLMO传感器转基因。因此,在miRNA加工因子的条件性敲除后未能观察到表型并不能可靠地表明miRNA在给定环境中缺乏关键作用。
Loss of Drosophila mir-9a induces a subtle increase in sensory bristles, but a substantial loss of wing tissue. Here, we establish that the latter phenotype is largely due to ectopic apoptosis in the dorsal wing primordium, and we could rescue wing development in the absence of this microRNA by dorsal-specific inhibition of apoptosis. Such apoptosis was a consequence of de-repressing Drosophila LIM-only (dLMO), which encodes a transcriptional regulator of wing and neural development. We observed cell-autonomous elevation of endogenous dLMO and a GFP-dLMO 3'UTR sensor in mir-9a mutant wing clones, and heterozygosity for dLMO rescued the apoptosis and wing defects of mir-9a mutants. We also provide evidence that dLMO, in addition to senseless, contributes to the bristle defects of the mir-9a mutant. Unexpectedly, the upregulation of dLMO, loss of Cut, and adult wing margin defects seen with mir-9a mutant clones were not recapitulated by clonal loss of the miRNA biogenesis factors Dicer-1 or Pasha, even though these mutant conditions similarly de-repressed miR-9a and dLMO sensor transgenes. Therefore, the failure to observe a phenotype upon conditional knockout of a miRNA processing factor does not reliably indicate the lack of critical roles of miRNAs in a given setting.
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