Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously required for early ventral endoderm morphogenesis.
Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously required for early ventral endoderm morphogenesis.
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DOI：
10.1242/bio.2012040
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发表时间：
2012-03-15
期刊：
影响因子：
2.4
通讯作者：
Evans SM
中科院分区：
文献类型：
--
作者：
Harrelson Z;Kaestner KH;Evans SM
中轴中内胚层由脊索前板和脊索组成。缺乏合适的Cre驱动程序阻碍了从遗传学上剖析这些组件中的每一个或其中表达的基因对前部模式的需求的能力。在这里，我们已经利用Isl 1-Cre翼螺旋转录因子Foxa 2的作用，特别是在前索板和腹侧内胚层。Foxa2loxP/loxP; Isl 1-Cre突变体在13.5 dpc死亡，表现出前神经管和前脑模式的畸变，以及腹侧前肠形态发生和心脏融合。Foxa 2loxP/loxP; Isl 1-Cre突变体的分子分析表明，Foxa 2是表达脊索和背侧前肠内胚层标记Shh所需的Isl 1谱系。Brachyury和Hlxb 9。我们的研究结果支持Foxa 2在脊索前板脊索形态发生，轴向图案，背侧前肠内胚层的图案的要求。腹侧内胚层中Foxa 2的缺失导致Sox 17、Gata 4和ZO蛋白的表达减少，至少部分解释了所观察到的前肠融合缺乏、贲门裂和腹侧内胚层凋亡增加。
Axial mesendoderm is comprised of prechordal plate and notochord. Lack of a suitable Cre driver has hampered the ability to genetically dissect the requirement for each of these components, or genes expressed within them, to anterior patterning. Here, we have utilized Isl1-Cre to investigate roles of the winged helix transcription factor Foxa2 specifically in prechordal plate and ventral endoderm. Foxa2loxP/loxP; Isl1-Cre mutants died at 13.5 dpc, exhibiting aberrations in anterior neural tube and forebrain patterning, and in ventral foregut morphogenesis and cardiac fusion. Molecular analysis of Foxa2loxP/loxP; Isl1-Cre mutants indicated that Foxa2 is required in Isl1 lineages for expression of notochord and dorsal foregut endoderm markers, Shh. Brachyury, and Hlxb9. Our results support a requirement for Foxa2 in prechordal plate for notochord morphogenesis, axial patterning, and patterning of dorsal foregut endoderm. Loss of Foxa2 in ventral endoderm resulted in reduced expression of Sox17, Gata4, and ZO proteins, accounting at least in part for observed lack of foregut fusion, cardia bifida, and increased apoptosis of ventral endoderm.
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