LIM homeodomain transcription factor Isl1 directs normal pyloric development by targeting Gata3.
LIM homeodomain transcription factor Isl1 directs normal pyloric development by targeting Gata3.
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LIM 同源域转录因子 Isl1 通过靶向 Gata3 指导正常幽门发育
DOI：
10.1186/1741-7007-12-25
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发表时间：
2014-03-27
期刊：
影响因子：
5.4
通讯作者：
Cui S
中科院分区：
文献类型：
--
作者：
Li Y;Pan J;Wei C;Chen J;Liu Y;Liu J;Zhang X;Evans SM;Cui Y;Cui S
幽门发育或幽门收缩功能异常可导致十二指肠内容物反流入胃，增加胃化生和胃癌的风险。幽门区的切除也与先天性缺陷有关，例如相对常见的新生儿肥厚性幽门狭窄和原发性胃反流。因此，了解幽门的发育具有重要的临床意义。在这里，我们调查的LIM同源结构域转录因子Isl 1在幽门development.ResultsExamination的作用，Isl 1的表达在发展中的小鼠胃免疫组化，全Mountin原位杂交和实时定量PCR表明，Isl 1是高度表达在发展中的小鼠胃，主要是在幽门平滑肌层。免疫荧光法检测了人肥厚性幽门狭窄组织中Isl 1的表达，发现绝大多数平滑肌细胞表达Isl 1。Isl 1基因敲除小鼠模型研究了Isl 1在胚胎胃发育中的功能，Isl 1缺陷导致胚胎18.5天幽门外纵肌层几乎完全缺失，这与Gata 3基因敲除小鼠表型一致。染色质免疫沉淀、荧光素酶分析和电泳迁移率改变分析表明，Isl 1通过直接靶向Gata 3来保证幽门的正常发育。结论Isl 1-Gata 3转录调控轴是幽门正常发育所必需的。这些发现与临床高度相关，可能有助于更好地了解导致幽门疾病的途径。
BackgroundAbnormalities in pyloric development or in contractile function of the pylorus cause reflux of duodenal contents into the stomach and increase the risk of gastric metaplasia and cancer. Abnormalities of the pyloric region are also linked to congenital defects such as the relatively common neonatal hypertrophic pyloric stenosis, and primary duodenogastric reflux. Therefore, understanding pyloric development is of great clinical relevance. Here, we investigated the role of the LIM homeodomain transcription factor Isl1 in pyloric development.ResultsExamination of Isl1 expression in developing mouse stomach by immunohistochemistry, whole mountin situhybridization and real-time quantitative PCR demonstrated that Isl1 is highly expressed in developing mouse stomach, principally in the smooth muscle layer of the pylorus. Isl1 expression was also examined by immunofluorescence in human hypertrophic pyloric stenosis where the majority of smooth muscle cells were found to express Isl1.Isl1function in embryonic stomach development was investigated utilizing a tamoxifen-inducibleIsl1knockout mouse model.Isl1deficiency led to nearly complete absence of the pyloric outer longitudinal muscle layer at embryonic day 18.5, which is consistent withGata3null mouse phenotype. Chromatin immunoprecipitation, luciferase assays, and electrophoretic mobility shift assays revealed that Isl1 ensures normal pyloric development by directly targetingGata3.ConclusionsThis study demonstrates that the Isl1-Gata3transcription regulatory axis is essential for normal pyloric development. These findings are highly clinically relevant and may help to better understand pathways leading to pyloric disease.
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DOI：
10.1083/jcb.107.6.2341
发表时间：
1988-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aufderheide E;Ekblom P
通讯作者：
Ekblom P
影响因子：
64.8
作者：
Laugwitz, KL;Moretti, A;Chien, KR
通讯作者：
Chien, KR
影响因子：
3.6
作者：
Hermans, D;Sokal, EM;Buts, JP
通讯作者：
Buts, JP
DOI：
10.1016/j.gep.2010.12.007
发表时间：
2011-03
期刊：
Gene expression patterns : GEP
影响因子：
--
作者：
Das P;May CL
通讯作者：
May CL
影响因子：
64.8
作者：
KARLSSON, O;THOR, S;EDLUND, T
通讯作者：
EDLUND, T