Institute of Neurosciences, Miguel Hernández University-Spanish National Research Council, 03550 San Juan, Alicante, Spain.
J Neurosci. 2013 Feb 27;33(9):3967-80. doi: 10.1523/JNEUROSCI.0726-12.2013.
The structural complexity of the brain depends on precise molecular and cellular regulatory mechanisms orchestrated by regional morphogenetic organizers. The thalamic organizer is the zona limitans intrathalamica (ZLI), a transverse linear neuroepithelial domain in the alar plate of the diencephalon. Because of its production of Sonic hedgehog, ZLI acts as a morphogenetic signaling center. Shh is expressed early on in the prosencephalic basal plate and is then gradually activated dorsally within the ZLI. The anteroposterior positioning and the mechanism inducing Shh expression in ZLI cells are still partly unknown, being a subject of controversial interpretations. For instance, separate experimental results have suggested that juxtaposition of prechordal (rostral) and epichordal (caudal) neuroepithelium, anteroposterior encroachment of alar lunatic fringe (L-fng) expression, and/or basal Shh signaling is required for ZLI specification. Here we investigated a key role of Wnt signaling in the molecular regulation of ZLI positioning and Shh expression, using experimental embryology in ovo in the chick. Early Wnt expression in the ZLI regulates Gli3 and L-fng to generate a permissive territory in which Shh is progressively induced by planar signals of the basal plate.
大脑的结构复杂性取决于由区域形态发生组织者协调的精确分子和细胞调节机制。丘脑组织者是丘脑限界内区(ZLI),它是神经上皮的一个横向线性区域,位于间脑的翼板中。由于其产生的 Sonic hedgehog,ZLI 充当形态发生信号中心。Shh 在脑前基板的早期表达,然后在 ZLI 中逐渐向背部激活。ZLI 细胞中 Shh 表达的前后定位和诱导机制仍部分未知,这是一个有争议的解释的主题。例如,独立的实验结果表明,前脑(头侧)和表皮神经上皮(尾侧)的并列、翼状狂躁边(L-fng)表达的前后侵袭,以及/或基底 Shh 信号对于 ZLI 的指定是必需的。在这里,我们使用鸡胚的实验胚胎学研究了 Wnt 信号在 ZLI 定位和 Shh 表达的分子调节中的关键作用。ZLI 中的早期 Wnt 表达调节 Gli3 和 L-fng,以产生一个允许的区域,其中 Shh 被基板的平面信号逐渐诱导。