Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors.
Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors.
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DOI：
10.1038/ncomms14666
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发表时间：
2017-03-10
影响因子：
16.6
通讯作者：
Pasterkamp RJ
中科院分区：
文献类型：
--
作者：
Jongbloets BC;Lemstra S;Schellino R;Broekhoven MH;Parkash J;Hellemons AJ;Mao T;Giacobini P;van Praag H;De Marchis S;Ramakers GM;Pasterkamp RJ
导向蛋白Semaphorin 7A（Sema 7A）是免疫系统和神经系统正常发育所必需的。尽管Sema 7A在成熟大脑中有很强的表达，但其在成年人中的作用仍然不清楚。在这里，我们表明，Sema 7A利用不同的细胞表面受体来控制成年海马齿状回（DG），神经发生的成熟大脑的选择区域之一的神经祖细胞的增殖和分化。丛蛋白C1选择性表达于成年小鼠DG的早期神经祖细胞，并介导Sema 7A对祖细胞增殖的抑制作用。随后，在成年出生的DG颗粒细胞的分化过程中，Sema 7A通过含有β1-亚基的整合素受体促进树突生长、复杂性和棘发育。我们的数据确定Sema 7A作为成人海马神经发生的关键调节因子，提供了一个例子，说明不同的受体使用时空控制和多样化的成人大脑中的指导线索的影响。脑信号蛋白在成年人大脑中的功能知之甚少。在这里，作者表明，Sema 7A通过不同的受体使用在成年海马中执行阶段特异性功能;在祖细胞中，Sema 7A通过作用于丛蛋白C1抑制增殖，而在成年神经元中，它通过β1-整合素促进树突生长。
The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neural progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexity and spine development through β1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain. The functions of semaphorins in the adult brain are poorly understood. Here the authors show that Sema7A carries out stage-specific functions in the adult hippocampus via differential receptor usage; in progenitor cells, Sema7A inhibits proliferation via acting on PlexinC1, whereas in adult-born neurons, it promotes dendrite growth through β1-integrins.