Developmental guidance of embryonic corneal innervation: Roles of Semaphorin3A and Slit2
Developmental guidance of embryonic corneal innervation: Roles of Semaphorin3A and Slit2
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DOI：
10.1016/j.ydbio.2010.04.032
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发表时间：
2010-08-01
影响因子：
2.7
通讯作者：
Linsenmayer, Thomas F.
中科院分区：
文献类型：
--
作者：
Kubilus, James K.;Linsenmayer, Thomas F.
在发育中的鸡胚中，角膜是体内神经分布最密集的结构之一，来自眼三叉神经节(OTG)的神经在一系列空间和时间调节事件中支配角膜，然而，关于调节这些事件的信号知之甚少，这里我们研究了轴突引导分子Semaphorin3A和SLIT2的参与。对早期角膜及其受体Neuropilin-1和Robo2的表达分析表明，Semaphorin 3A和Slit2都参与了阻止神经进入角膜基质直到适当的时间(即它们起到负调节作用)的过程，对它们的受体的分析支持这一结论。在发育的后期，Semaphorin3A的表达再次与它作为负调节因子的作用一致，这一次它是进入角膜上皮的神经的负调节因子。然而，在这个阶段对Robo2的表达分析提出了这样一种可能性，Slit2已经从负调节因子转变为支持这种转换的正调节因子，功能分析-通过添加重组Slit2蛋白或免疫中和Slit2抗体-表明在早期Slit2负调节OTG神经的生长，而在后期它通过增加角膜上皮内神经分支来正调节神经的生长(C)2010 Elsevier Inc.保留所有权利
The cornea is one of the most densely innervated structures of the body In the developing chicken embryo, nerves from the ophthalmic trigeminal ganglion (OTG) innervate the cornea in a series of spatially and temporally regulated events However, little is known concerning the signals that regulate these events Here we have examined the involvement of the axon guidance molecules Semaphorin3A and Slit2. and their respective receptors, Neuropilin-1 and Robo2 Expression analyses of early corneas suggest an involvement of both Semaphorin3A and Slit2 in preventing nerves from entering the corneal stroma until the proper time (i.e. they serve as negative regulators), and analyses of their receptors support this conclusion. At later stages of development the expression of Semaphorin3A is again consistent with its serving as a negative regulator this time for nerves entering the corneal epithelium However, expression analyses of Robo2 at this stage raised the possibility that Slit2 had switched from a negative regulator to a positive regulator In support of such a switch, functional analyses-by addition of recombinant Slit2 protein or immunoneutralization with a Slit2 antibody-showed that at an early stage Slit2 negatively regulates the outgrowth of nerves from the OTG, whereas at the later stage it positively regulated the growth of nerves by increasing nerve branching within the corneal epithelium (C) 2010 Elsevier Inc All rights reserved