Non-cell autonomous control of precerebellar neuron migration by Slit and Robo proteins
Non-cell autonomous control of precerebellar neuron migration by Slit and Robo proteins
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DOI：
10.1242/dev.150375
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发表时间：
2018-01-01
期刊：
影响因子：
4.6
通讯作者：
Chedotal, Alain
中科院分区：
文献类型：
--
作者：
Dominici, Chloe;Rappeneau, Quentin;Chedotal, Alain
在发育过程中，小脑前神经元从后脑背侧切向迁移到底板。它们的轴突穿过它，但它们的细胞体在到达中线时停止向腹侧迁移。以前已经表明，Slit化学排斥剂及其受体Robo1和Robo2可能以排斥的方式控制小脑前神经元的迁移。在这里，我们在小鼠中使用了条件性敲除策略来验证这一假设。我们发现，有针对性的失活表达的Robo1和Robo2受体在小脑前神经元不扰乱他们的迁移，他们仍然停止在中线。选择性消融底板细胞中所有三种Slit蛋白的表达对脑桥神经元没有影响，并且仅诱导一小部分下橄榄神经元穿过底板的迁移。同样，我们发现面神经核中Slit蛋白的表达与脑桥神经元迁移有关。总之，这些结果表明，Robo1和Robo2受体的行为非细胞自主迁移小脑前神经元和地板信号，而不是Slit蛋白，必须存在，以防止中线交叉。
During development, precerebellar neurons migrate tangentially from the dorsal hindbrain to the floor plate. Their axons cross it but their cell bodies stop their ventral migration upon reaching the midline. It has previously been shown that Slit chemorepellents and their receptors, Robo1 and Robo2, might control the migration of precerebellar neurons in a repulsive manner. Here, we have used a conditional knockout strategy in mice to test this hypothesis. We show that the targeted inactivation of the expression of Robo1 and Robo2 receptors in precerebellar neurons does not perturb their migration and that they still stop at the midline. The selective ablation of the expression of all three Slit proteins in floor-plate cells has no effect on pontine neurons and only induces the migration of a small subset of inferior olivary neurons across the floor plate. Likewise, we show that the expression of Slit proteins in the facial nucleus is dispensable for pontine neuron migration. Together, these results show that Robo1 and Robo2 receptors act non-cell autonomously in migrating precerebellar neurons and that floor-plate signals, other than Slit proteins, must exist to prevent midline crossing.