VEGF is required for dendritogenesis of newly born olfactory bulb interneurons
VEGF is required for dendritogenesis of newly born olfactory bulb interneurons
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DOI：
10.1242/dev.039636
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发表时间：
2010-01-15
期刊：
影响因子：
4.6
通讯作者：
Keshet, Eli
中科院分区：
文献类型：
--
作者：
Licht, Tamar;Eavri, Ronen;Keshet, Eli
血管生成因子血管内皮生长因子A（VEGF）已被证明在神经发生中发挥作用，但它如何影响成人神经发生尚未完全了解。为了描述VEGF在嗅球（OB）神经发生的连续阶段中的作用，我们使用了一种条件性转基因系统来抑制成年小鼠脑室下区（SVZ）、吻侧迁移流（RMS）和OB的VEGF信号传导，这些区域构成了各自的出生地点、迁移路线和新出生的中间神经元成熟并整合在现有OB电路中的地点。荧光标记的成人出生的神经元的发展后，我们表明，隔离的VEGF是组成性表达的不同类型的居民OB神经元极大地损害了传入SVZ出生的神经元树突发育。颗粒细胞树突棘密度降低，肾小球周围神经元树突明显缩短，分支减少。值得注意的是，当VEGF抑制延迟至出生后时，SVZ、RMS和OB的脉管系统和灌注没有受到不利影响，因此将VEGF对树突状细胞发生的作用与其在血管维持中的已知作用分开。此外，VEGF的需求是特定的新生神经元，因为已经建立的OB神经元不受VEGF抑制。因此，这项研究揭示了VEGF在成人大脑中的一个令人惊讶的灌注独立作用，即在成人出生的神经元的成熟中的重要作用。
The angiogenic factor vascular endothelial growth factor A (VEGF) has been shown to have a role in neurogenesis, but how it affects adult neurogenesis is not fully understood. To delineate a role for VEGF in successive stages of olfactory bulb (OB) neurogenesis, we used a conditional transgenic system to suppress VEGF signaling at the adult mouse sub-ventricular zone (SVZ), rostral migratory stream (RMS) and OB, which constitute the respective sites of birth, the migration route, and sites where newly born interneurons mature and integrate within the existing OB circuitry. Following the development of fluorescently tagged adult-born neurons, we show that sequestration of VEGF that is constitutively expressed by distinct types of resident OB neurons greatly impaired dendrite development in incoming SVZ-born neurons. This was evidenced by reduced dendritic spine density of granule cells and significantly shorter and less branched dendrites in periglomerular neurons. Notably, the vasculature and perfusion of the SVZ, RMS and OB were not adversely affected when VEGF suppression was delayed until after birth, thus uncoupling the effect of VEGF on dendritogenesis from its known role in vascular maintenance. Furthermore, a requirement for VEGF was specific to newly born neurons, as already established OB neurons were not damaged by VEGF inhibition. This study thus uncovered a surprising perfusion-independent role of VEGF in the adult brain, namely, an essential role in the maturation of adult-born neurons.