Comparative Analysis of Genes Regulated by Dzip1/iguana and Hedgehog in Zebrafish

Comparative Analysis of Genes Regulated by Dzip1/iguana and Hedgehog in Zebrafish
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DOI:
10.1002/dvdy.24237
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发表时间:
2015-02-01
影响因子:
2.5
通讯作者:
Childs, Sarah J.
Childs, Sarah J.
中科院分区:
生物学3区
文献类型:
--
作者:
Arnold, Corey R.;Lamont, Ryan E.;Childs, Sarah J.

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背景:斑马鱼遗传突变体鬣蜥(iguana,IGU)在纤毛基底体蛋白Dzip1中存在缺陷,导致纤毛形成不当。Dzip1还与Hedgehog(HH)下游的转录激活因子Gli蛋白相互作用,在IGU突变体中HH信号被破坏。HH控制着广泛的发育过程,包括稳定发育中的血管以防止出血。使用IGU突变胚胎和HH途径拮抗剂环丙胺处理的胚胎,我们进行了微阵列以确定参与HH信号调节血管稳定性的基因。结果:我们鉴定出40个基因在IGU突变体和环丙胺处理的胚胎中都有明显的表达变化。对于其中的一个子集,我们使用原位杂交来确定胚胎发育期间的定位,并确认在阵列上看到的表达变化。结论:通过比较血管不稳定遗传模型和化学抑制HH信号的基因表达变化,我们确定了一组在血管稳定中可能起作用的40个差异表达基因。《发展动力学》244:211-223,2015。(C)2015年Wiley期刊,Inc.关键发现
Background: The zebrafish genetic mutant iguana (igu) has defects in the ciliary basal body protein Dzip1, causing improper cilia formation. Dzip1 also interacts with the downstream transcriptional activators of Hedgehog (Hh), the Gli proteins, and Hh signaling is disrupted in igu mutants. Hh governs a wide range of developmental processes, including stabilizing developing blood vessels to prevent hemorrhage. Using igu mutant embryos and embryos treated with the Hh pathway antagonist cyclopamine, we conducted a microarray to determine genes involved in Hh signaling mediating vascular stability. Results: We identified 40 genes with significantly altered expression in both igu mutants and cyclopamine-treated embryos. For a subset of these, we used in situ hybridization to determine localization during embryonic development and confirm the expression changes seen on the array. Conclusions: Through comparing gene expression changes in a genetic model of vascular instability with a chemical inhibition of Hh signaling, we identified a set of 40 differentially expressed genes with potential roles in vascular stabilization. Developmental Dynamics 244:211-223, 2015. (c) 2015 Wiley Periodicals, Inc.Key Findings