成年哺乳動(dòng)物腦的“腦室下區(qū)”(SVZ)是細(xì)胞增殖的一個(gè)重要地方,，有助于神經(jīng)細(xì)胞自我更新和對(duì)受傷做出反應(yīng),。SVZ干細(xì)胞小環(huán)境保持有“神經(jīng)干細(xì)胞”(NSCs)和“神經(jīng)先祖細(xì)胞”(NPCs),，二者之間的平衡是正常腦發(fā)育的關(guān)鍵,。
Notch信號(hào)作用已知調(diào)控NSC自我更新,，而EGFR (外皮生長(zhǎng)因子受體)信號(hào)作用影響NPC增殖,。Aguirre等人發(fā)現(xiàn),，這些通道相互作用,，來通過由EGFR調(diào)節(jié)的對(duì)Notch信號(hào)作用的調(diào)控維持NSC 和 NPC細(xì)胞群之間的平衡。這一發(fā)現(xiàn)指出了可以作為目標(biāo)來在受傷后增強(qiáng)NSCs 或 NPCs生成的特定信號(hào)通道,。
延伸閱讀：
Neuron：神經(jīng)干細(xì)胞腦內(nèi)移動(dòng)機(jī)制
日本名古屋市立大學(xué)研究人員在的美國(guó)科學(xué)雜志《神經(jīng)元》網(wǎng)絡(luò)版上發(fā)表文章指出,，他們?cè)诶美鲜筮M(jìn)行實(shí)驗(yàn)時(shí)，發(fā)現(xiàn)其腦內(nèi)新產(chǎn)生的神經(jīng)干細(xì)胞在腦內(nèi)移動(dòng)的機(jī)制,。這一發(fā)現(xiàn)可能有助于開發(fā)治療腦梗塞等腦部疾病的新方法,。
此前，研究人員已經(jīng)知道神經(jīng)干細(xì)胞主要存在于成年哺乳動(dòng)物側(cè)腦室的室管膜下區(qū),，在正常情況下處于“蟄伏”狀態(tài),，在腦部受到損傷等特殊情況下，神經(jīng)干細(xì)胞可以增殖,、遷移并且分化成新的神經(jīng)元和神經(jīng)膠質(zhì)細(xì)胞,，然后在腦的不同部位發(fā)揮相應(yīng)作用，比如使受到損傷的部位再生或者發(fā)育成與嗅覺等感覺有關(guān)的細(xì)胞,。但是,，這些神經(jīng)干細(xì)胞在細(xì)胞密布的腦內(nèi)是如何移動(dòng)的,，一直未被專家了解清楚。
名古屋市立大學(xué)的再生醫(yī)學(xué)教授澤本和延率領(lǐng)的研究小組發(fā)現(xiàn),，老鼠腦內(nèi)新產(chǎn)生的神經(jīng)干細(xì)胞在通過腦內(nèi)分布最廣的星形膠質(zhì)細(xì)胞間隙時(shí),，會(huì)分泌一種名為“SLIT”的蛋白質(zhì)，受到這種蛋白質(zhì)刺激后,，星形膠質(zhì)細(xì)胞就會(huì)把自身凸起的部分收縮回去,，從而為神經(jīng)干細(xì)胞讓出一條通道，使神經(jīng)干細(xì)胞得以在腦內(nèi)移動(dòng),。星形膠質(zhì)細(xì)胞是哺乳動(dòng)物腦內(nèi)分布最廣泛的一類細(xì)胞,，該細(xì)胞伸出的許多長(zhǎng)且分叉的凸起物充填在各種神經(jīng)細(xì)胞之間，起支持和分隔神經(jīng)細(xì)胞的作用,。
研究人員進(jìn)而通過操作使老鼠的神經(jīng)干細(xì)胞無法分泌“SLIT”蛋白質(zhì),，結(jié)果發(fā)現(xiàn)神經(jīng)干細(xì)胞的移動(dòng)速度變得非常緩慢，星形膠質(zhì)細(xì)胞也不再為其讓路,，這說明正是“SLIT”蛋白質(zhì)使神經(jīng)干細(xì)胞能夠在腦內(nèi)順利移動(dòng),。
在下一階段的研究中，名古屋市立大學(xué)的研究者將嘗試開發(fā)讓神經(jīng)干細(xì)胞高效移動(dòng)到指定部位的新方法,，以期更好地治療腦梗塞等腦部疾病,。
生物谷推薦原文出處：
Nature doi:10.1038/nature09347
Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal
Adan Aguirre,Maria E. Rubio& Vittorio Gallo
Specialized cellular microenvironments, or ‘niches’, modulate stem cell properties, including cell number, self-renewal and fate decisions1, 2. In the adult brain, niches that maintain a source of neural stem cells (NSCs) and neural progenitor cells (NPCs) are the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus3, 4, 5. The size of the NSC population of the SVZ at any time is the result of several ongoing processes, including self-renewal, cell differentiation, and cell death. Maintaining the balance between NSCs and NPCs in the SVZ niche is critical to supply the brain with specific neural populations, both under normal conditions or after injury. A fundamental question relevant to both normal development and to cell-based repair strategies in the central nervous system is how the balance of different NSC and NPC populations is maintained in the niche. EGFR (epidermal growth factor receptor) and Notch signalling pathways have fundamental roles during development of multicellular organisms6. In Drosophila and in Caenorhabditis elegans these pathways may have either cooperative or antagonistic functions7, 8, 9. In the SVZ, Notch regulates NSC identity and self-renewal, whereas EGFR specifically affects NPC proliferation and migration10, 11, 12, 13. This suggests that interplay of these two pathways may maintain the balance between NSC and NPC numbers. Here we show that functional cell–cell interaction between NPCs and NSCs through EGFR and Notch signalling has a crucial role in maintaining the balance between these cell populations in the SVZ. Enhanced EGFR signalling in vivo results in the expansion of the NPC pool, and reduces NSC number and self-renewal. This occurs through a non-cell-autonomous mechanism involving EGFR-mediated regulation of Notch signalling. Our findings define a novel interaction between EGFR and Notch pathways in the adult SVZ, and thus provide a mechanism for NSC and NPC pool maintenance.
