Post-transcriptional regulation of the E/Daughterless ortholog HLH-2, negative feedback, and birth order bias during the AC/VU decision in C-elegans
Post-transcriptional regulation of the E/Daughterless ortholog HLH-2, negative feedback, and birth order bias during the AC/VU decision in C-elegans
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DOI：
10.1101/gad.1160803
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发表时间：
2003-12-15
影响因子：
10.5
通讯作者：
Greenwald, I
中科院分区：
文献类型：
--
作者：
Karp, X;Greenwald, I
秀丽隐杆线虫中的锚细胞/腹侧子宫前体细胞（AC/VU）决定是lin-12/Notch介导的侧向特化的典型例子。两个最初等价的细胞通过受体LIN-12及其配体LAG-2相互作用，使得一个成为AC，另一个成为VU。在这种相互作用过程中，反馈环放大lin-12活性的微小差异，限制lin-12转录到假定的VU和lag-2转录到假定的AC。在这里，我们发现，hlh-2似乎是所需的VU的命运，并直接激活滞后2转录在推定的AC。HLH-2似乎在lin-12或lag-2的差异转录之前选择性地积累在推定的AC中，因此是经历AC/VU决定的两个细胞之间最早可检测的差异。HLH-2在推定AC中的有限积累反映了HLH-2在推定VU中的转录后下调。我们的观察结果表明，hlh-2的负反馈，下调滞后-2转录在推定的VU的一部分。最后，我们表明，AC/VU的决定在一个单独的雌雄同体是有偏见的相对出生顺序的两个细胞，使第一个出生的细胞更有可能成为VU。我们提出的模型，建议如何出生顺序，HLH-2的积累，和转录滞后-2可能是在AC/VU的决定。
The anchor cell/ventral uterine precursor cell (AC/VU) decision in Caenorhabditis elegans is a canonical example of lin-12/Notch-mediated lateral specification. Two initially equivalent cells interact via the receptor LIN-12 and its ligand LAG-2, so that one becomes the AC and the other a VU. During this interaction, feedback loops amplify a small difference in lin-12 activity, limiting lin-12 transcription to the presumptive VU and lag-2 transcription to the presumptive AC. Here, we find that hlh-2 appears to be required for the VU fate and directly activates lag-2 transcription in the presumptive AC. HLH-2 appears to accumulate selectively in the presumptive AC prior to differential transcription of lin-12 or lag-2, and is therefore the earliest detectable difference between the two cells undergoing the AC/VU decision. The restricted accumulation of HLH-2 to the presumptive AC reflects post-transcriptional down-regulation of HLH-2 in the presumptive VU. Our observations suggest that hlh-2 is regulated as part of the negative feedback that down-regulates lag-2 transcription in the presumptive VU. Finally, we show that the AC/VU decision in an individual hermaphrodite is biased by the relative birth order of the two cells, so that the first-born cell is more likely to become the VU. We propose models to suggest how birth order, HLH-2 accumulation, and transcription of lag-2 may be linked during the AC/VU decision.