VEGF-A and neuropilin 1 (NRP1) shape axon projections in the developing CNS via dual roles in neurons and blood vessels.
VEGF-A and neuropilin 1 (NRP1) shape axon projections in the developing CNS via dual roles in neurons and blood vessels.
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DOI：
10.1242/dev.151621
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发表时间：
2017-07-01
期刊：
影响因子：
--
通讯作者：
Ruhrberg C
中科院分区：
文献类型：
--
作者：
Erskine L;François U;Denti L;Joyce A;Tillo M;Bruce F;Vargesson N;Ruhrberg C
视觉信息通过视网膜神经节细胞（RGC）轴突从眼睛传递到大脑。缺乏 NRP1 或 NRP1 结合 VEGF-A 亚型的小鼠具有 RGC 轴突组织缺陷以及脑血管缺陷。目前尚不清楚轴突缺陷是否完全是由 RGC 中 VEGF-A 信号传导缺陷引起的，还是因血管形态异常而加剧。具有 Brn3bCre 敲入等位基因的 RGC 中的靶向 NRP1 消融减少了视交叉处的轴突中线交叉和视束束颤。相比之下，Tie2-Cre 介导的内皮 NRP1 消融在视束中诱导轴突禁区，而不损害轴突交叉。在 Vegfa120/120 和 Vegfa188/188 小鼠中观察到类似的缺陷，这些小鼠由于表达单一 VEGF-A 同种型而具有血管缺陷。内皮 Nrp1 和 Vegfa188/188 突变体中的异位中线血管形成导致交叉内出现额外的轴突禁区。由于体外和体内测定表明血管不会排斥轴突，异常大或异位定位的血管可能对轴突生长造成物理障碍。我们的结论是，大脑发育过程中正确的轴突布线取决于神经血管共模式的精确分子控制。摘要：NRP1 在视网膜神经节细胞和血管内皮细胞中发挥双重作用，沿着小鼠视网膜和间脑之间的视神经通路组织轴突。
Visual information is relayed from the eye to the brain via retinal ganglion cell (RGC) axons. Mice lacking NRP1 or NRP1-binding VEGF-A isoforms have defective RGC axon organisation alongside brain vascular defects. It is not known whether axonal defects are caused exclusively by defective VEGF-A signalling in RGCs or are exacerbated by abnormal vascular morphology. Targeted NRP1 ablation in RGCs with a Brn3bCre knock-in allele reduced axonal midline crossing at the optic chiasm and optic tract fasciculation. In contrast, Tie2-Cre-mediated endothelial NRP1 ablation induced axon exclusion zones in the optic tracts without impairing axon crossing. Similar defects were observed in Vegfa120/120 and Vegfa188/188 mice, which have vascular defects as a result of their expression of single VEGF-A isoforms. Ectopic midline vascularisation in endothelial Nrp1 and Vegfa188/188 mutants caused additional axonal exclusion zones within the chiasm. As in vitro and in vivo assays demonstrated that vessels do not repel axons, abnormally large or ectopically positioned vessels are likely to present physical obstacles to axon growth. We conclude that proper axonal wiring during brain development depends on the precise molecular control of neurovascular co-patterning. Summary: NRP1 plays a dual role in retinal ganglion cells and in vascular endothelial cells to organise axons along the optic pathway between the mouse retina and diencephalon.
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影响因子：
16.6
作者：
Himmels P;Paredes I;Adler H;Karakatsani A;Luck R;Marti HH;Ermakova O;Rempel E;Stoeckli ET;Ruiz de Almodóvar C
通讯作者：
Ruiz de Almodóvar C
DOI：
10.1242/dev.113746
发表时间：
2015-12-15
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
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通讯作者：
McCarty JH
影响因子：
16.6
作者：
Aspalter IM;Gordon E;Dubrac A;Ragab A;Narloch J;Vizán P;Geudens I;Collins RT;Franco CA;Abrahams CL;Thurston G;Fruttiger M;Rosewell I;Eichmann A;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
16.2
作者：
Kuwajima T;Yoshida Y;Takegahara N;Petros TJ;Kumanogoh A;Jessell TM;Sakurai T;Mason C
通讯作者：
Mason C
DOI：
10.1242/dev.063362
发表时间：
2011-09
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Cariboni A;Davidson K;Dozio E;Memi F;Schwarz Q;Stossi F;Parnavelas JG;Ruhrberg C
通讯作者：
Ruhrberg C