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一系列时序性的同源异形基因活性促进了秀丽隐杆线虫特定阶段的发育事件。

A temporal sequence of heterochronic gene activities promotes stage-specific developmental events in Caenorhabditis elegans.

机构信息

Department of Molecular Biology, Rowan-Virtua School of Translational Biomedical Engineering & Sciences, Rowan University, Stratford, NJ 08084, USA.

出版信息

G3 (Bethesda). 2024 Aug 7;14(8). doi: 10.1093/g3journal/jkae130.

Abstract

The heterochronic genes of the nematode Caenorhabditis elegans control the succession of postembryonic developmental events. The 4 core heterochronic genes lin-14, lin-28, hbl-1, and lin-41 act in a sequence to specify cell fates specific to each of the 4 larval stages. It was previously shown that lin-14 has 2 activities separated in time that promote L1 and L2 developmental events, respectively. Using the auxin-inducible degron system, we find that lin-28 and hbl-1 each have 2 activities that control L2 and L3 events which are also separated in time. Relative to events they control, both lin-28 and hbl-1 appear to act just prior to or concurrently with events of the L2. Relative to each other, lin-28 and hbl-1 appear to act simultaneously. By contrast, the lin-14 activity controlling L2 events precedes those of lin-28 and hbl-1 controlling the same events, suggesting that lin-14's regulation of lin-28 is responsible for the delay. Likewise, the activities of lin-28 and hbl-1 controlling L3 fates act well in advance of those fates, suggesting a similar regulatory gap. lin-41 acts early in the L3 to affect fates of the L4, although it was not possible to determine whether it too has 2 temporally separated activities. We also uncovered a feedback phenomenon that prevents the reactivation of heterochronic gene activity late in development after it has been downregulated. This study places the heterochronic gene activities into a timeline of postembryonic development relative to one another and to the developmental events whose timing they control.

摘要

线虫 Caenorhabditis elegans 的异型基因控制着胚胎后发育事件的顺序。4 个核心异型基因 lin-14、lin-28、hbl-1 和 lin-41 按顺序作用,分别指定每个幼虫阶段特有的细胞命运。以前已经表明 lin-14 有 2 个时间上分开的活性,分别促进 L1 和 L2 发育事件。使用生长素诱导的降解结构域系统,我们发现 lin-28 和 hbl-1 各自具有 2 种活性,分别控制 L2 和 L3 事件,这些事件在时间上也是分开的。相对于它们控制的事件,lin-28 和 hbl-1 似乎都在 L2 事件之前或与 L2 事件同时发生。彼此相比,lin-28 和 hbl-1 似乎同时发生。相比之下,控制 L2 事件的 lin-14 活性先于 lin-28 和 hbl-1 控制相同事件的活性,表明 lin-14 对 lin-28 的调节导致了延迟。同样,lin-28 和 hbl-1 控制 L3 命运的活性远远早于这些命运的活性,表明存在类似的调节差距。lin-41 在 L3 早期作用于 L4 的命运,尽管尚无法确定它是否也具有 2 个时间上分开的活性。我们还发现了一种反馈现象,即在异型基因活性被下调后,它在发育后期会阻止异型基因活性的重新激活。这项研究将异型基因活性置于胚胎后发育的时间线上,相对于彼此以及它们控制的发育事件的时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fea/11304605/456d1a7699e4/jkae130f1.jpg

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