Molecular interactions coordinating the development of the forebrain and face
Molecular interactions coordinating the development of the forebrain and face
复制标题
DOI：
10.1016/j.ydbio.2005.04.030
复制
发表时间：
2005-08-01
影响因子：
2.7
通讯作者：
Helms, JA
中科院分区：
文献类型：
--
作者：
Marcucio, RS;Cordero, DR;Helms, JA
从建筑学的角度来看，前脑作为一个框架，在其上的中，上部的脸发展和增长。除了服务的结构作用，我们提出的证据表明，前脑是一个信号的来源，形状的面部骨骼。在这项研究中，我们抑制了来自神经外胚层的Sonic hedgehog（Shh）信号，然后检查了治疗引起的分子变化和骨骼改变。我们注意到的第一个变化是前脑的背腹极性被扰乱，表现为腹侧端脑Shh的丢失，腹侧标记NkX2.1和D1x2的表达减少，以及伴随的背侧标记Pax6的扩展。除了前脑神经外胚层的变化，我们观察到改变的基因表达模式，在面部外胚层。例如，Shh在额鼻外胚层中不被诱导，而Ptc和Gli1在外胚层和相邻间充质中均被减少。结果，额鼻隆突的信号中心被破坏，隆突未能进行proximodistal和mediolateral扩张。发育15天后，处理过的胚胎的上喙被截短，并且骨骼元件相对于下颌元件的骨骼元件位于更中间和近端的位置。这些数据表明，Shh在前脑中的作用是调节Shh在面部的表达，并且这些Shh结构域共同介导了额鼻突内的图案化和中面部和上面部的proximodistal生长。(c)2005年爱思唯尔公司All rights reserved.
From an architectural point of view, the forebrain acts as a framework upon which the middle and upper face develops and grows. In addition to serving a structural role, we present evidence that the forebrain is a source of signals that shape the facial skeleton. In this study, we inhibited Sonic hedgehog (Shh) signaling from the neuroectoderm then examined the molecular changes and the skeletal alterations resulting from the treatment. One of the first changes we noted was that the dorsoventral polarity of the forebrain was disturbed, which manifested as a loss of Shh in the ventral telencephalon, a reduction in expression of the ventral markers NkX2.1 and D1x2, and a concomitant expansion of the dorsal marker Pax6. In addition to changes in the forebrain neuroectoderm, we observed altered gene expression pattern,; in the facial ectoderm. For example, Shh was not induced in the frontonasal ectoderm, and Ptc and Gli1 were reduced in both the ectoderm and adjacent mesenchyme. As a consequence, a signaling center in the frontonasal prominence was disrupted and the prominence failed to undergo proximodistal and mediolateral expansion. After 15 days of development, the upper beaks of the treated embryos were truncated, and the skeletal elements were located in more medial and proximal locations in relation to the skeletal elements of the lower jaw elements. These data indicate that a role of Shh in the forebrain is to regulate Shh expression in the face, and that together, these Shh domains mediate patterning within the frontonasal prominence and proximodistal outgrowth of the middle and upper face. (c) 2005 Elsevier Inc. All rights reserved.