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星形胶质细胞中ErbB2的重新诱导促进成年大脑皮质中的放射状胶质祖细胞特性。

Reinduction of ErbB2 in astrocytes promotes radial glial progenitor identity in adult cerebral cortex.

作者信息

Ghashghaei H T, Weimer Jill M, Schmid Ralf S, Yokota Yukako, McCarthy Ken D, Popko Brian, Anton E S

机构信息

University of North Carolina Neuroscience Center and the Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.

出版信息

Genes Dev. 2007 Dec 15;21(24):3258-71. doi: 10.1101/gad.1580407.

Abstract

Radial glial cells play a critical role in the construction of mammalian brain by functioning as a source of new neurons and by providing a scaffold for radial migration of new neurons to their target locations. Radial glia transform into astrocytes at the end of embryonic development. Strategies to promote functional recovery in the injured adult brain depend on the generation of new neurons and the appropriate guidance of these neurons to where they are needed, two critical functions of radial glia. Thus, the competence to regain radial glial identity in the adult brain is of significance for the ability to promote functional repair via neurogenesis and targeted neuronal migration in the mature brain. Here we show that the in vivo induction of the tyrosine kinase receptor, ErbB2, in mature astrocytes enables a subset of them to regain radial glial identity in the mature cerebral cortex. These new radial glial progenitors are capable of giving rise to new neurons and can support neuronal migration. These studies indicate that ErbB2 signaling critically modulates the functional state of radial glia, and induction of ErbB2 in distinct adult astrocytes can promote radial glial identity in the mature cerebral cortex.

摘要

放射状胶质细胞在哺乳动物大脑构建中发挥着关键作用,它作为新神经元的来源,并为新神经元向其目标位置的放射状迁移提供支架。放射状胶质细胞在胚胎发育末期转变为星形胶质细胞。促进成年受损大脑功能恢复的策略依赖于新神经元的生成以及这些神经元向所需位置的适当引导,而这正是放射状胶质细胞的两项关键功能。因此,成年大脑中恢复放射状胶质细胞特性的能力对于通过神经发生和成熟大脑中靶向神经元迁移来促进功能修复的能力具有重要意义。在此我们表明,在成熟星形胶质细胞中体内诱导酪氨酸激酶受体ErbB2,能使其中一部分细胞在成熟大脑皮层中重新获得放射状胶质细胞特性。这些新的放射状胶质前体细胞能够产生新神经元,并能支持神经元迁移。这些研究表明,ErbB2信号通路关键地调节放射状胶质细胞的功能状态,在不同的成年星形胶质细胞中诱导ErbB2可促进成熟大脑皮层中的放射状胶质细胞特性。

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