Department of Molecular Biology, Rowan-Virtua School of Translational Biomedical Engineering & Sciences, Rowan University, Stratford, NJ 08084, USA.
G3 (Bethesda). 2024 Aug 7;14(8). doi: 10.1093/g3journal/jkae130.
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.
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。
