Developmental Gene Expression In C elegans

我们对影响发育的基因调控和信号通路的兴趣经常重叠。在秀丽隐杆线虫中，异时性途径以时间特异性方式控制多个发育事件。锌指转录因子LIN-29是这一途径的最下游效应子，在最后的幼虫阶段（L4）起作用，调节幼虫到成虫转换的元件。我们与艾森曼实验室（UMBC）合作，探索新的LIN-29靶点及其对这一发展转型的影响。我们使用RNA测序来鉴定在早期时间点错误表达LIN-29的动物和对照动物之间差异表达的基因。在230个LIN-29激活的基因中，我们发现编码角质层胶原蛋白的基因被过度表达。有趣的是，lin-29和其中一些胶原蛋白的表达在具有角质层损伤的成人中增加，表明lin-29在成人角质层维持中的先前未知的功能。另一方面，参与脂肪代谢的基因在350个LIN-29下调的靶点中富集。许多LIN-29抑制基因通常在肠道中表达，表明细胞非自主调节。我们确定了几个LIN-29上调基因编码的信号分子，可能作为介体的调节，在卵巢表达的基因编码的脂肪代谢酶和卵黄蛋白原。总体而言，我们的研究结果支持LIN-29作为成年角质层合成和完整性的主要调节剂的模型，以及作为从幼虫生命期间的快速生长到成年期的缓慢生长和后代生产的重要过渡中发生的代谢变化的触发器。

Our interests in gene regulation and signaling pathways influencing development often overlap. In Caenorhabditis elegans, the heterochronic pathway controls multiple developmental events in a time-specific manner. The most downstream effector of this pathway, the zinc-finger transcription factor LIN-29, acts in the last larval stage (L4) to regulate elements of the larval-to-adult switch. We collaborated with the Eisenmann Lab (UMBC) to explore new LIN-29 targets and their implications for this developmental transition. We used RNA-sequencing to identify genes differentially expressed between animals misexpressing LIN-29 at an early time point and control animals. Among 230 LIN-29-activated genes, we found that genes encoding cuticle collagens were overrepresented. Interestingly, expression of lin-29 and some of these collagens was increased in adults with cuticle damage, suggesting a previously unknown function for LIN-29 in adult cuticle maintenance. On the other hand, genes involved in fat metabolism were enriched among 350 LIN-29-downregulated targets. Many LIN-29-repressed genes are normally expressed in the intestine, suggesting cell-nonautonomous regulation. We identified several LIN-29 upregulated genes encoding signaling molecules that may act as mediators in the regulation of intestinally expressed genes encoding fat metabolic enzymes and vitellogenins. Overall, our results support the model of LIN-29 as a major regulator of adult cuticle synthesis and integrity, and as the trigger for metabolic changes that take place at the important transition from rapid growth during larval life to slower growth and offspring production during adulthood.