Chemoattractive activity of Sonic Hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb
Chemoattractive activity of Sonic Hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb
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DOI：
10.1634/stemcells.2008-0297
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发表时间：
2008-09-01
期刊：
影响因子：
5.2
通讯作者：
Traiffort, Elisabeth
中科院分区：
文献类型：
--
作者：
Angot, Elodie;Loulier, Karine;Traiffort, Elisabeth
成人室下区(SVZ)支持神经干细胞的自我更新和分化，并在整个成年生活中不断地产生新的神经元。神经母细胞通过头端迁移流(RMS)从SVZ向嗅球(OB)迁移的机制已被广泛研究，但控制神经母细胞从SVZ向嗅球迁移的因素尚不清楚。形态原Sonic Hedgehog(Shh)对神经干细胞具有增殖和存活活性，是一种轴突趋化物质，在发育过程中参与引导连合轴突的形成。在这里，我们发现在成年小鼠的SVZ提取液和脑脊液中存在Shh蛋白，并且我们证明SVZ和RMS中的迁移神经母细胞表达Shh受体Patted。我们发现Shh在体外对SVZ来源的神经前体细胞显示出趋化活性，这种作用被平滑的拮抗剂Cur61414所阻断。有趣的是，表达Shh的细胞移植到成年小鼠的RMS上方，对体内迁移的神经母细胞具有趋化活性，从而导致它们的聚集和偏离正常的迁移途径。此外，将Shh腺病毒转移到侧脑室，或用其生理拮抗剂Hedgehog相互作用蛋白或中和Shh抗体阻断成年小鼠SVZ中存在的Shh，提供了Shh可以保留SVZ来源的神经母细胞的体内证据。通过Shh的趋化活性调节离开SVZ并到达OB的神经母细胞数量的能力表明，这个成体干细胞生态位的细胞迁移具有新的可塑性。
The adult subventricular zone (SVZ) supports neural stem cell self-renewal and differentiation and continually gives rise to new neurons throughout adult life. The mechanisms orienting the migration of neuroblasts from the SVZ to the olfactory bulb (OB) via the rostral migratory stream (RMS) have been extensively studied, but factors controlling neuroblast exit from the SVZ remain poorly explored. The morphogen Sonic Hedgehog (Shh) displays proliferative and survival activities toward neural stem cells and is an axonal chemoattractant implicated in guidance of commissural axons during development. We identify here the presence of Shh protein in SVZ extracts and in the cerebrospinal fluid of adult mice, and we demonstrate that migrating neuroblasts in the SVZ and RMS express the Shh receptor Patched. We show that Shh displays a chemoattractive activity in vitro on SVZ-derived neuronal progenitors, an effect blocked by Cur61414, a Smoothened antagonist. Interestingly, Shh-expressing cells grafted above the RMS of adult mice exert a chemoattractive activity on migrating neuroblasts in vivo, thus inducing their accumulation and deviation from their normal migratory pathway. Furthermore, the adenoviral transfer of Shh into the lateral ventricle or the blocking of Shh present in the SVZ of adult mice using its physiological antagonist Hedgehog interacting protein or neutralizing Shh antibodies provides in vivo evidence that Shh can retain SVZ-derived neuroblasts. The ability to modulate the number of neuroblasts leaving the SVZ and reaching the OB through the chemoattractive activity of Shh suggests a novel degree of plasticity in cell migration of this adult stem cell niche.