Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis
Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis
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DOI：
10.1016/j.ydbio.2006.03.053
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发表时间：
2006-07-15
影响因子：
2.7
通讯作者：
Evans, Sylvia
中科院分区：
文献类型：
--
作者：
Lin, Lizhu;Bu, Lei;Evans, Sylvia
LIM 同源域转录因子 Islet1 (Isl1) 在前肠内胚层和心源性中胚层中表达，是心脏发育最早阶段所必需的。在这里，我们报告说，Shh 的上游也需要 isl1。我们发现，在 isl1 缺失小鼠中，前肠内胚层中的 Sonic Hedgehog (Shh) 下调。 Shh 信号通过独特的平滑激活受体 (Smo) 发出。为了研究刺猬信号在 isl1 结构域中的作用，我们利用 isl1-cre 消除了 smo。 Isl1-cre;smo 突变体表现出与 Shh 无效小鼠中观察到的心血管缺陷相似的心血管缺陷，定义了 isl1 表达域内的 hedgehog 信号传导对主动脉弓和流出道形成的空间要求。主动脉弓和流出道的形成需要通过神经毡蛋白受体 npn1 和 npn2 进行信号蛋白信号传导。我们发现 is11-cre;smo 突变体中 npn2 的表达下调，表明影响心脏前极形态发生所需的 isl1/Shh/npn 途径。 (c) 2006 Elsevier Inc. 保留所有权利。
The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in both foregut endoderm and cardiogenic mesoderm and is required for earliest stages of heart development. Here, we report that isl1 is also required upstream of Shh. We find that, in isl1 null mice, Sonic hedgehog (Shh) is downregulated in foregut endoderm. Shh signals through the unique activating receptor smoothened (Smo). To investigate the role of hedgehog signaling in the isl1 domain, we ablated smo utilizing isl1-cre. Isl1-cre;smo mutants exhibit cardiovascular defects similar to those observed in Shh null mice, defining a spatial requirement for hedgehog signaling within isl1 expression domains for aortic arch and outflow tract formation. Semaphorin signaling through neuropilin receptors npn1 and npn2 is required for aortic arch and outflow tract formation. We find that expression of npn2 is downregulated in is11-cre;smo mutants, suggestingan isl1/Shh/npn pathway required to affect morphogenesis at the anterior pole of the heart. (c) 2006 Elsevier Inc. All rights reserved.