N-cadherin acts in concert with Slit1-Robo2 signaling in regulating aggregation of placode-derived cranial sensory neurons
N-cadherin acts in concert with Slit1-Robo2 signaling in regulating aggregation of placode-derived cranial sensory neurons
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DOI：
10.1242/dev.034355
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发表时间：
2009-12-15
期刊：
影响因子：
4.6
通讯作者：
Bronner-Fraser, Marianne
中科院分区：
文献类型：
--
作者：
Shiau, Celia E.;Bronner-Fraser, Marianne
脊椎动物的颅感觉神经节具有神经嵴和外胚层基板的双重起源。在其中最大的三叉神经节中，Slit 1-Robo 2信号传导对于适当的神经节组装至关重要。在这里，我们证明了细胞粘附分子N-钙粘蛋白及其与Slit 1-Robo 2在体内神经节形成过程中的相互作用的关键作用。鸡三叉神经节和鳃上神经节的一个共同特征是基板神经元上的N-cadherin和Robo 2以及神经嵴细胞上的Slit 1的表达。有趣的是，在神经节组装过程中，N-钙粘蛋白定位于基板神经元之间的细胞间粘附连接。N-钙粘蛋白的耗尽导致适当的神经节聚结的损失，类似于Robo 2丢失后观察到的情况，这表明这两种途径可能交叉。与这种可能性相一致，阻断或增强Slit-Robo信号传导调节基板细胞表面上的N-钙粘蛋白表达，伴随基板粘附的改变。总N-钙粘蛋白mRNA或蛋白水平缺乏明显变化提示翻译后调节。N-钙粘蛋白与显性负性Robo的共表达消除了分散神经节的Robo 2功能丧失表型，而N-钙粘蛋白的丧失逆转了由Slit-Robo表达增加诱导的异常聚集。我们的研究提出了一种新的机制，即N-钙粘蛋白与Slit-Robo信号一起介导适当神经节发生所需的基板细胞粘附。
Vertebrate cranial sensory ganglia have a dual origin from the neural crest and ectodermal placodes. In the largest of these, the trigeminal ganglion, Slit1-Robo2 signaling is essential for proper ganglion assembly. Here, we demonstrate a crucial role for the cell adhesion molecule N-cadherin and its interaction with Slit1-Robo2 during gangliogenesis in vivo. A common feature of chick trigeminal and epibranchial ganglia is the expression of N-cadherin and Robo2 on placodal neurons and Slit1 on neural crest cells. Interestingly, N-cadherin localizes to intercellular adherens junctions between placodal neurons during ganglion assembly. Depletion of N-cadherin causes loss of proper ganglion coalescence, similar to that observed after loss of Robo2, suggesting that the two pathways might intersect. Consistent with this possibility, blocking or augmenting Slit-Robo signaling modulates N-cadherin protein expression on the placodal cell surface concomitant with alteration in placodal adhesion. Lack of an apparent change in total N-cadherin mRNA or protein levels suggests post-translational regulation. Co-expression of N-cadherin with dominant-negative Robo abrogates the Robo2 loss-of-function phenotype of dispersed ganglia, whereas loss of N-cadherin reverses the aberrant aggregation induced by increased Slit-Robo expression. Our study suggests a novel mechanism whereby N-cadherin acts in concert with Slit-Robo signaling in mediating the placodal cell adhesion required for proper gangliogenesis.