EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion
EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion
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DOI：
10.1387/ijdb.082777na
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发表时间：
2009-01-01
影响因子：
0.7
通讯作者：
Copp, Andrew J.
中科院分区：
文献类型：
--
作者：
Abdul-Aziz, Noraishah M.;Turmaine, Mark;Copp, Andrew J.
神经褶粘连和融合的分子基础是神经形成的一个知之甚少的方面。细胞表面糖基磷脂酰肌醇（GPI）锚定蛋白已涉及神经折叠粘附，鉴于在缺乏ephrinA 5或EphA 7受体的小鼠中观察到的颅神经管缺陷，ephrinAs是特别有吸引力的候选物。在这里，我们证明ephrinsA 1，A3和A4，以及几个EphA受体，表达在关闭的小鼠脊髓神经管。大多数ephrinAs和EphA受体被发现在尾部区域的多个组织中表达，而EphA 2受体特异性地表达在神经管融合开始之前的神经褶皱的顶端。利用小鼠全胚胎培养，我们发现GPI锚定分子从胚胎细胞表面裂解导致脊髓神经管闭合延迟。将EphA 1和EphA 3融合蛋白经神经内注射到培养的胚胎中用于特异性破坏ephrinA-EphA受体相互作用，并导致脊髓神经管闭合的抑制，而对生长或发育进程没有不利影响。这些处理不会干扰神经板弯曲或神经褶升高，这两者对于脊髓神经管闭合都是至关重要的。我们的研究结果表明，ephrinA-EphA受体的相互作用所需的小鼠脊髓神经管的关闭，并支持假设ephrinA-EphA受体的相互作用可能参与的分子识别事件，最终在脊髓神经形成过程中的神经褶皱的尖端的粘附和融合。
The molecular basis of neural fold adhesion and fusion is a poorly understood aspect of neurulation. Cell surface glycosyl phosphatidylinositol (GPI)-anchored proteins have been implicated in neural fold adhesion, with ephrinAs particularly attractive candidates in view of the cranial neural tube defects observed in mice lacking ephrinA5 or the EphA7 receptor. Here, we demonstrate that ephrinsA1, A3 and A4, as well as several EphA receptors, are expressed in the closing mouse spinal neural tube. Most ephrinAs and EphA receptors were found to be expressed in multiple tissues in the caudal region, whereas EphA2 receptor was expressed specifically at the apices of the neural folds just prior to onset of neural tube fusion. Using mouse whole embryo culture, we found that cleavage of GPI-anchored molecules from the embryonic cell surface resulted in delay of spinal neural tube closure. Injection of EphA1 and EphA3 fusion proteins intraamniotically into cultured embryos was used to specifically disrupt ephrinA-EphA receptor interactions, and led to inhibition of spinal neural tube closure, without adverse effects on growth or developmental progression. These treatments did not disturb neural plate bending or neural fold elevation, both of which are critical for spinal neural tube closure. Our findings demonstrate that ephrinA-EphA receptor interactions are required for closure of the mouse spinal neural tube, and support the hypothesis that ephrinA-EphA receptor interactions may participate in the molecular recognition events that culminate in adhesion and fusion of the tips of the neural folds during spinal neurulation.