Role of the homeodomain transcription factor Bapx1 in mouse distal stomach development.
Role of the homeodomain transcription factor Bapx1 in mouse distal stomach development.
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DOI：
10.1053/j.gastro.2009.01.009
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发表时间：
2009-05
期刊：
影响因子：
29.4
通讯作者：
Zimmer WE
中科院分区：
文献类型：
--
作者：
Verzi MP;Stanfel MN;Moses KA;Kim BM;Zhang Y;Schwartz RJ;Shivdasani RA;Zimmer WE
内胚层的扩张和图案化在脊椎动物中产生高度有序的多器官消化系统。在前肠远端衍生物中，胃体、胃窦、幽门和十二指肠是边界清晰的独特结构。在肠道间充质中表达的一些同源结构域转录因子传递消化道前后模式所需的位置信息。Barx 1尤其控制胃的分化和形态发生。NK同源框基因Bapx 1（Nkx 3 -2）在骨骼发育中具有既定的作用，但其在哺乳动物肠道中的功能尚不清楚。我们产生了一个Bapx 1Cre基因敲入等位基因的命运地图Bapx 1表达细胞，并评估其在胃肠道发育中的功能。表达Bapx 1的细胞分布在胃后胃的吻侧边界的肠间充质中，靠近胃体和胃窦的交界处。平滑肌分化和分布的早期区域标志物是表面上正常的Bapx 1Cre/Cre肠，但有独特的形态学异常附近的吻Bapx 1域：胃窦段的胃明显缩短和幽门收缩丢失。在单一和复合的Barx 1和Bapx 1突变小鼠的胃表型的表达域和检查的比较表明这两个因素之间的层次结构; Bapx 1的表达丢失在没有Barx 1。这项研究揭示了Bapx 1在远端胃发育中的非冗余需求，将其置于Barx 1依赖性途径中，并说明了肠道间充质同源盒基因对内胚层分化和消化器官发生的普遍影响。
Expansion and patterning of the endoderm generate a highly ordered, multi-organ digestive system in vertebrate animals. Among distal foregut derivatives, the gastric corpus, antrum, pylorus and duodenum are distinct structures with sharp boundaries. Some homeodomain transcription factors expressed in gut mesenchyme convey positional information required for anterior-posterior patterning of the digestive tract. Barx1, in particular, controls stomach differentiation and morphogenesis. The NK homeobox gene Bapx1 (Nkx3-2) has an established role in skeletal development but its function in the mammalian gut is less clear. We generated a Bapx1Cre knock-in allele to fate map Bapx1-expressing cells and evaluate its function in gastrointestinal development. Bapx1-expressing cells populate the gut mesenchyme with a rostral boundary in the hindstomach, near the junction of the gastric corpus and antrum. Smooth muscle differentiation and distribution of early regional markers are ostensibly normal in Bapx1Cre/Cre gut, but there are distinctive morphologic abnormalities near this rostral Bapx1 domain: the antral segment of the stomach is markedly shortened and the pyloric constriction is lost. Comparison of expression domains and examination of stomach phenotypes in single and compound Barx1 and Bapx1 mutant mice suggest a hierarchy between these two factors; Bapx1 expression is lost in the absence of Barx1. This study reveals the non-redundant requirement for Bapx1 in distal stomach development, places it within a Barx1-dependent pathway, and illustrates the pervasive influence of gut mesenchyme homeobox genes on endoderm differentiation and digestive organogenesis.
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