Slits are chemorepellents endogenous to hypothalamus and steer thalamocortical axons into ventral telencephalon.
Slits are chemorepellents endogenous to hypothalamus and steer thalamocortical axons into ventral telencephalon.
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DOI：
10.1093/cercor/bhp035
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
O'Leary DD
中科院分区：
文献类型：
--
作者：
Braisted JE;Ringstedt T;O'Leary DD
丘脑皮质轴突（Thalamocortical axons，TCAs）起源于背侧丘脑，沿着丘脑外侧表面向腹侧延伸，当它们接近下丘脑时，转向腹侧进入端脑。体外研究表明，下丘脑释放TCA的化学排斥剂，敲除小鼠的分析表明，Slit化学排斥剂及其受体Robo 2影响TCA寻路。我们发现，狭缝化学排斥是下丘脑的化学排斥，并通过机器人引导TCA到腹侧端脑。在TCA寻路过程中，Slit 1和Slit 2在下丘脑和腹侧丘脑中表达，Robo 1和Robo 2在背侧丘脑中表达。在背侧丘脑和Slit 2表达细胞的胶原凝胶共培养物中，轴突数量和长度在面向Slit 2表达细胞的外植体侧减少，总体轴突生长减少，并且轴突转向远离Slit 2表达细胞。因此，Slit 2是背侧丘脑轴突的抑制剂和化学排斥剂。背侧丘脑与活间脑切片的胶原凝胶共培养物，有和没有下丘脑部分覆盖有Robo 2-fc表达细胞以阻断Slit功能，将Slit鉴定为下丘脑化学排斥剂。因此，裂缝是下丘脑内源性TCA的化学排斥剂，并将TCA从间脑引导到腹侧端脑，这是Slit和Robo 2突变小鼠中有缺陷的关键寻路事件。
Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures of dorsal thalamus with sections of live diencephalon, with and without the hypothalamus portion overlaid with Robo2-fc-expressing cells to block Slit function, identify Slits as the hypothalamic chemorepellent. Thus, Slits are chemorepellents for TCAs endogenous to hypothalamus and steer TCAs from diencephalon into ventral telencephalon, a critical pathfinding event defective in Slit and Robo2 mutant mice.
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