Cadherin-7 and cadherin-6B differentially regulate the growth, branching and guidance of cranial motor axons
Cadherin-7 and cadherin-6B differentially regulate the growth, branching and guidance of cranial motor axons
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DOI：
10.1242/dev.042457
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发表时间：
2010-03-01
期刊：
影响因子：
4.6
通讯作者：
Guthrie, Sarah C.
中科院分区：
文献类型：
--
作者：
Barnes, Sarah H.;Price, Stephen R.;Guthrie, Sarah C.
钙粘蛋白-7（Cad 7）和钙粘蛋白-6B（Cad 6 B）分别在颅运动神经元发育的早期和晚期表达。cad 7在颅运动神经元产生后不久就被表达，以及在其轴突延伸的环境中表达。相比之下，Cad 6 B由成熟的颅运动神经元表达。我们证明，在鸡，这些钙粘蛋白发挥不同的作用，在颅运动轴突形态，分支和投影。使用体外方法，我们表明，Cad 7增强运动轴突生长，抑制多个轴突的形成，并限制间质分支，从而促进分化运动神经元的单一无分支轴突特征的发展。相反，Cad 6 B在体外促进运动轴突分支，这是成熟运动神经元的特征。这些钙粘蛋白的体内功能获得和丧失实验产生了与这种解释一致的表型。特别是，钙粘蛋白介导的相互作用在体内的损失导致颅运动神经元正常分支程序失调，并引起轴突导航缺陷。我们还表明，Cad 6 B功能通过磷脂酰肌醇3-激酶途径。总之，这些数据表明，Cad 7和Cad 6 B差异调节颅运动神经元的生长，分支和轴突导向。
Cadherin-7 (Cad7) and cadherin-6B (Cad6B) are expressed in early and late phases of cranial motoneuron development, respectively. Cad7 is expressed by cranial motoneurons soon after they are generated, as well as in the environment through which their axons extend. By contrast, Cad6B is expressed by mature cranial motoneurons. We demonstrate in chick that these cadherins play distinct roles in cranial motor axon morphology, branching and projection. Using in vitro approaches, we show that Cad7 enhances motor axon outgrowth, suppresses the formation of multiple axons and restricts interstitial branching, thus promoting the development of a single unbranched axon characteristic of differentiating motoneurons. Conversely, Cad6B in vitro promotes motor axon branching, a characteristic of mature motoneurons. In vivo gain-and loss-of-function experiments for these cadherins yielded phenotypes consistent with this interpretation. In particular, a loss of cadherin-mediated interactions in vivo led to dysregulation of the cranial motoneuron normal branching programme and caused axon navigation defects. We also demonstrate that Cad6B functions via the phosphatidylinositol 3-kinase pathway. Together, these data show that Cad7 and Cad6B differentially regulate cranial motoneuron growth, branching and axon guidance.