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脏壁中胚层板决定脾脏和胰腺的左右定位,并受Bapx1/Nkx3.2调控。

The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3.2.

作者信息

Hecksher-Sørensen Jacob, Watson Robert P, Lettice Laura A, Serup Palle, Eley Lorraine, De Angelis Carlo, Ahlgren Ulf, Hill Robert E

机构信息

Comparative and Developmental Genetics Section, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

出版信息

Development. 2004 Oct;131(19):4665-75. doi: 10.1242/dev.01364. Epub 2004 Aug 25.

Abstract

The mechanism by which left-right (LR) information is interpreted by organ primordia during asymmetric morphogenesis is largely unknown. We show that spleen and pancreatic laterality is dependent on a specialised, columnar mesodermal-derived cell layer referred to here as the splanchnic mesodermal plate (SMP). At early embryonic stages, the SMP is bilateral, surrounding the midline-located stomach and dorsal pancreatic bud. Under control of the LR asymmetry pathway, the left SMP is maintained and grows laterally. Mice carrying the dominant hemimelia (Dh) mutation lack the SMP. Significantly, the mice are asplenic and the pancreas remains positioned along the embryonic midline. In the absence of Fgf10 expression, the spleno-pancreatic mesenchyme and surrounding SMP grow laterally but contain no endodermal component, showing that leftward growth is autonomous and independent of endoderm. In the Bapx1(-/-) mutants, the SMP is defective. Normally, the SMP is a source for both Fgf9 and Fgf10; however, in the Bapx1 mutant, Fgf10 expression is downregulated and the dorsal pancreas remains at the midline. We conclude that the SMP is an organiser responsible for the leftward growth of the spleno-pancreatic region and that Bapx1 regulates SMP functions required for pancreatic laterality.

摘要

在不对称形态发生过程中,器官原基解读左右(LR)信息的机制在很大程度上尚不清楚。我们发现脾脏和胰腺的定位依赖于一种特殊的、柱状中胚层来源的细胞层,在此称为脏壁中胚层板(SMP)。在胚胎早期阶段,SMP是双侧的,围绕位于中线的胃和背侧胰腺芽。在LR不对称信号通路的控制下,左侧SMP得以维持并向侧面生长。携带显性半肢畸形(Dh)突变的小鼠缺乏SMP。值得注意的是,这些小鼠无脾,胰腺仍沿胚胎中线定位。在缺乏Fgf10表达的情况下,脾-胰腺间充质和周围的SMP向侧面生长,但不包含内胚层成分,这表明向左生长是自主的,且不依赖于内胚层。在Bapx1(-/-)突变体中,SMP存在缺陷。正常情况下,SMP是Fgf9和Fgf10的来源;然而,在Bapx1突变体中,Fgf10表达下调,背侧胰腺仍位于中线。我们得出结论,SMP是一个组织者,负责脾-胰腺区域的向左生长,并且Bapx1调节胰腺定位所需的SMP功能。

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