Genomewide expression analysis in zebrafish mind bomb alleles with pancreas defects of different severity identifies putative Notch responsive genes.
Genomewide expression analysis in zebrafish mind bomb alleles with pancreas defects of different severity identifies putative Notch responsive genes.
复制标题
斑马鱼思维炸弹等位基因中的全基因组表达分析具有不同严重程度的胰腺缺陷，鉴定了推定的凹口反应性基因。
DOI：
10.1371/journal.pone.0001479
复制
发表时间：
2008-01-23
期刊：
影响因子：
3.7
通讯作者：
Jiang YJ
中科院分区：
文献类型：
--
作者：
Hegde A;Qiu NC;Qiu X;Ho SH;Tay KQ;George J;Ng FS;Govindarajan KR;Gong Z;Mathavan S;Jiang YJ
Notch信号是一种进化保守的发育途径。斑马鱼大脑炸弹（mib）突变体携带mib基因突变，该基因编码通过Delta/Jagged泛素化和内化激活Notch所需的RING E3连接酶。我们使用原位杂交和胰腺特异性GFP系的GFP表达分析来检测mib突变体在胰腺发育中的缺陷，对三种不同的mib突变等位基因进行了全局基因表达谱分析，并使用实时PCR和荧光双原位杂交验证了微阵列数据。我们的研究表明，mib突变体外分泌胰腺减少，这种缺陷在mibta52b中最严重，其次是mibm132，然后是mitfi91，这与在相应的mib突变等位基因中发现的Notch活性降低是一致的。mib突变体的全局表达谱分析表明，wt和三个mib突变等位基因的基因表达谱存在显著差异。这三个mib等位基因共有91个差异表达基因。通过对微阵列数据的详细分析，我们已经确定了几个先前表征的基因和一些推测的notch反应基因参与胰腺发育。此外，实时PCR和荧光双原位杂交的结果与微阵列数据基本一致。这项研究首次提供了mib突变体的全球基因表达谱，产生了有用的基因组资源，并为鉴定参与Notch信号传导和Notch调控发育过程的新基因的功能提供了机会。
Notch signaling is an evolutionarily conserved developmental pathway. Zebrafish mind bomb (mib) mutants carry mutations on mib gene, which encodes a RING E3 ligase required for Notch activation via Delta/Jagged ubiquitylation and internalization. We examined the mib mutants for defects in pancreas development using in situ hybridization and GFP expression analysis of pancreas-specific GFP lines, carried out the global gene expression profile analysis of three different mib mutant alleles and validated the microarray data using real-time PCR and fluorescent double in situ hybridization. Our study showed that the mib mutants have diminished exocrine pancreas and this defect was most severe in mibta52b followed by mibm132 and then mibtfi91, which is consistent with the compromised Notch activity found in corresponding mib mutant alleles. Global expression profile analysis of mib mutants showed that there is a significant difference in gene expression profile of wt and three mib mutant alleles. There are 91 differentially expressed genes that are common to all three mib alleles. Through detailed analysis of microarray data, we have identified several previously characterized genes and some putative Notch-responsive genes involved in pancreas development. Moreover, results from real-time PCR and fluorescent double in situ hybridization were largely consistent with microarray data. This study provides, for the first time, a global gene expression profile in mib mutants generating useful genomic resources and providing an opportunity to identify the function of novel genes involved in Notch signaling and Notch-regulated developmental processes.
登录
查看更多内容
影响因子：
4.6
作者：
Esni, F;Ghosh, B;Leach, SD
通讯作者：
Leach, SD
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
10.5
作者：
BAILEY, AM;POSAKONY, JW
通讯作者：
POSAKONY, JW
影响因子：
56.9
作者：
Hirata, H;Yoshiura, S;Kageyama, R
通讯作者：
Kageyama, R
影响因子：
19
作者：
Chong, SW;Jiang, YJ
通讯作者：
Jiang, YJ