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PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells

机译:PACAP / PAC1自分泌系统促进神经祖细胞的增殖和星形胶质细胞生成

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摘要

The Pituitary adenylate cyclase-activating peptide (PACAP) ligand/type 1 receptor (PAC1) system regulates neuro-genesis and gliogenesis. It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs-mediated cAMP-dependent signaling pathway. However, it is unknown whether this ligand/receptor system has a function in proliferation of NPCs. In this study, we identified that PACAP and PAC1 were highly expressed and co-localized in NPCs of mouse cortex at embryonic day 14.5 (E14.5) and found that the PACAP/PAC1 system potentiated growth factor-induced proliferation of mouse cortical NPCs at E14.5 via Gq-, but not Gs-, mediated PLC/IP3-dependent signaling pathway in an autocrine manner. Moreover, PAC1 activation induced elongation of cellular processes and a stellate morphology in astrocytes that had the bromodeoxyuridine (BrdU)-incorporating ability of NPCs. Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling. These results suggest that the PACAP/PAC1 system may play a dual role in neural/glial progenitor cells not only differentiation but 2 also proliferation in the cortical astrocyte lineage via Ca2+-dependent signaling pathways through PAC1. (c) 2006 Wiley-Liss, Inc.
机译:垂体腺苷酸环化酶激活肽(PACAP)配体/ 1型受体(PAC1)系统调节神经发生和神经胶质发生。公认的是,PACAP / PAC1系统通过Gs介导的cAMP依赖性信号通路诱导神经祖细胞(NPC)分化。然而,未知该配体/受体系统是否具有在NPC增殖中的功能。在这项研究中,我们确定PACAP和PAC1在胚胎第14.5天(E14.5)在小鼠皮质的NPC中高表达和共定位,并发现PACAP / PAC1系统在小鼠的大脑皮层NPC处增强了生长因子诱导的增殖。 E14.5以自分泌方式通过Gq-而非Gs-介导的依赖PLC / IP3的信号传导途径。此外,PAC1激活诱导星形胶质细胞具有NPC的溴脱氧尿苷(BrdU)整合能力的细胞过程的延长和星状形态。与此想法一致,我们确定大多数BrdU阳性NPC通过PAC1信号传导分化为星形胶质细胞。这些结果表明,PACAP / PAC1系统不仅在神经/神经胶质祖细胞的分化中起着双重作用,而且在经由Ca2 +依赖的PAC1信号通路在皮质星形胶质细胞系中的增殖也起着双重作用。 (c)2006年Wiley-Liss,Inc.

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