Conserved expression of mouse Six1 in the pre-placodal region (PPR) and identification of an enhancer for the rostral PPR.
Conserved expression of mouse Six1 in the pre-placodal region (PPR) and identification of an enhancer for the rostral PPR.
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DOI：
10.1016/j.ydbio.2010.04.029
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发表时间：
2010-08
影响因子：
2.7
通讯作者：
Shigeru Sato;K. Ikeda;G. Shioi;H. Ochi;H. Ogino;H. Yajima;K. Kawakami
中科院分区：
文献类型：
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作者：
Shigeru Sato;K. Ikeda;G. Shioi;H. Ochi;H. Ogino;H. Yajima;K. Kawakami
所有脊椎动物的颅感觉器官和感觉神经元都是从颅基板发育而来的。在鸡，两栖动物和斑马鱼，所有基板起源于一个共同的前体结构域，基板前区（PPR），标志着Six 1/4和Eya 1/2的表达。然而，PPR从未在哺乳动物中描述过，并且PPR形成的机制也不清楚。在这里，我们报告的马蹄形小鼠外胚层周围的前神经板的模式大致类似于非哺乳类脊椎动物的Six 1的表达。为了阐明Six 1阳性小鼠外胚层的身份，我们通过体内增强子测定寻找负责Six 1表达的增强子。一个保守的非编码序列，Six 1 -14，表现出特定的增强子活性，在喙PPR的鸡和爪蟾和小鼠外胚层。这些结果有力地表明PPR在小鼠中的存在，并且它在脊椎动物中是保守的。此外，我们显示了Six 1 -14，Six 1吻侧PPR增强子，增强子活性的同源结构域蛋白结合位点的重要性，并且Dlx 5，Msx 1和Pax 7是调节Six 1表达水平和面积的候选结合因子，从而调节PPR的位置。我们的研究结果提供了重要的信息和工具，以阐明早期感觉发育的分子机制，并对感觉前体/干细胞的发展具有影响。
All cranial sensory organs and sensory neurons of vertebrates develop from cranial placodes. In chick, amphibians and zebrafish, all placodes originate from a common precursor domain, the pre-placodal region (PPR), marked by the expression of Six1/4 and Eya1/2. However, the PPR has never been described in mammals and the mechanism involved in the formation of PPR is poorly defined. Here, we report the expression of Six1 in the horseshoe-shaped mouse ectoderm surrounding the anterior neural plate in a pattern broadly similar to that of non-mammalian vertebrates. To elucidate the identity of Six1-positive mouse ectoderm, we searched for enhancers responsible for Six1 expression by in vivo enhancer assays. One conserved non-coding sequence, Six1-14, showed specific enhancer activity in the rostral PPR of chick and Xenopus and in the mouse ectoderm. These results strongly suggest the presence of PPR in mouse and that it is conserved in vertebrates. Moreover, we show the importance of the homeodomain protein-binding sites of Six1-14, the Six1 rostral PPR enhancer, for enhancer activity, and that Dlx5, Msx1 and Pax7 are candidate binding factors that regulate the level and area of Six1 expression, and thereby the location of the PPR. Our findings provide critical information and tools to elucidate the molecular mechanism of early sensory development and have implications for the development of sensory precursor/stem cells.