Nature:神经干细胞的平衡

来源:Nature 发布时间:2010年09月16日 浏览次数: 【字体: 收藏 打印文章

成年哺乳动物脑的“脑室下区”(SVZ)是细胞增殖的一个重要地方,有助于神经细胞自我更新和对受伤做出反应。SVZ干细胞小环境保持有“神经干细胞”(NSCs)和“神经先祖细胞”(NPCs),二者之间的平衡是正常脑发育的关键。

Notch信号作用已知调控NSC自我更新,而EGFR (外皮生长因子受体)信号作用影响NPC增殖。Aguirre等人发现,这些通道相互作用,来通过由EGFR调节的对Notch信号作用的调控维持NSC 和 NPC细胞群之间的平衡。这一发现指出了可以作为目标来在受伤后增强NSCs 或 NPCs生成的特定信号通道。

原文出处:

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.

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