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一项在 中进行的基因表达筛选鉴定了卵子发生过程中新型 JAK/STAT 和 EGFR 靶标。

A Gene Expression Screen in Identifies Novel JAK/STAT and EGFR Targets During Oogenesis.

机构信息

Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544

出版信息

G3 (Bethesda). 2019 Jan 9;9(1):47-60. doi: 10.1534/g3.118.200786.

Abstract

The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) and epidermal growth factor receptor (EGFR) signaling pathways are conserved regulators of tissue patterning, morphogenesis, and other cell biological processes. During oogenesis, these pathways determine the fates of epithelial follicle cells (FCs). JAK/STAT and EGFR together specify a population of cells called the posterior follicle cells (PFCs), which signal to the oocyte to establish the embryonic axes. In this study, whole genome expression analysis was performed to identify genes activated by JAK/STAT and/or EGFR. We observed that 317 genes were transcriptionally upregulated in egg chambers with ectopic JAK/STAT and EGFR activity in the FCs. The list was enriched for genes encoding extracellular matrix (ECM) components and ECM-associated proteins. We tested 69 candidates for a role in axis establishment using RNAi knockdown in the FCs. We report that the signaling protein Semaphorin 1b becomes enriched in the PFCs in response to JAK/STAT and EGFR. We also identified () as a novel target of JAK/STAT in the FCs that regulates egg chamber shape. mRNA becomes enriched at the anterior and posterior poles of the egg chamber at stages 6 to 7 and is regulated by JAK/STAT. Altering expression in the poles or middle of the egg chamber produces rounder egg chambers. We propose that regulates egg shape by remodeling the basement membrane.

摘要

Janus 激酶/信号转导和转录激活因子(JAK/STAT)和表皮生长因子受体(EGFR)信号通路是组织模式形成、形态发生和其他细胞生物学过程的保守调节因子。在卵子发生过程中,这些途径决定了上皮滤泡细胞(FCs)的命运。JAK/STAT 和 EGFR 共同指定了一个称为后滤泡细胞(PFCs)的细胞群体,它们向卵母细胞发出信号,以建立胚胎轴。在这项研究中,进行了全基因组表达分析,以鉴定被 JAK/STAT 和/或 EGFR 激活的基因。我们观察到,在 FC 中异位 JAK/STAT 和 EGFR 活性的卵囊中,有 317 个基因转录上调。该列表富含编码细胞外基质(ECM)成分和 ECM 相关蛋白的基因。我们使用 FC 中的 RNAi 敲低测试了 69 个候选基因在轴建立中的作用。我们报告说,信号蛋白 Semaforin 1b 在响应 JAK/STAT 和 EGFR 时在 PFCs 中富集。我们还确定了 () 作为 FC 中 JAK/STAT 的一个新靶标,它调节卵室形状。 在 6 到 7 阶段,mRNA 在卵室的前后极富集,并受 JAK/STAT 调控。改变卵室极或中部的 表达会产生更圆的卵室。我们提出,通过重塑基底膜来调节卵的形状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1cb/6325903/fb459895fd94/47f1.jpg

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