Developmental Gene Expression In C elegans

线虫的发育基因表达

• 批准号: 10250040
• 负责人: Michael Krause
• 金额: $ 29.85万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10250040
• 关键词: Adult; Anatomy; Animals; Biological Models; Caenorhabditis elegans; Cell Fate Control; Cells; Collagen; Control Animal; Development; Developmental Gene; Elements; Enzymes; Event; Fatty acid glycerol esters; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Growth; Human; Human Development; Intestines; Knowledge; Laboratories; Life; Lobular Neoplasia; Logic; Maintenance; Mediator of activation protein; Metabolic; Modeling; Mutation; Nematoda; Pathway interactions; Phenotype; Production; Regulation; Role; Signal Pathway; Signaling Molecule; System; Systems Development; Time; Tissues; Transcriptional Regulation; Vitellogenins; Zinc Fingers; cell type; differential expression; interest; lipid metabolism; offspring; rapid growth; transcription factor; transcriptome sequencing

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.

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，异慢性途径以特定时间的方式控制多种发育事件。该途径最下游的效应因子是锌指转录因子LIN-29，它在幼虫的最后阶段（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靶点及其对这种发育转变的影响。我们使用rna测序来鉴定早期错误表达LIN-29的动物与对照动物之间的基因表达差异。在230个lin -29激活基因中，我们发现编码角质层胶原蛋白的基因过多。有趣的是，在角质层损伤的成人中，lin-29和其中一些胶原蛋白的表达增加，这表明lin-29在成人角质层维护中具有以前未知的功能。另一方面，参与脂肪代谢的基因在350个lin -29下调的靶标中富集。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。我们发现了几个编码信号分子的LIN-29上调基因，这些基因可能作为调节肠道表达的编码脂肪代谢酶和卵黄蛋白原的基因的介质。总体而言，我们的研究结果支持LIN-29作为成虫角质层合成和完整性的主要调节因子的模型，以及在幼虫生活期间从快速生长到成年期较慢生长和后代生产的重要转变中发生的代谢变化的触发器。