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

¹ 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; ² Department of Molecular Biomedical Sciences, School of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27607, USA; ³ Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27704, USA; ⁴ Department of Pharmacology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA; ⁵ The Jack Miller Center for Peripheral Neuropathy, Department of Neurology, The University of Chicago, Chicago, Illinois 60637, USA

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.

[Keywords: Cortical development; neurogenesis; radial glia; ErbB receptors; neuregulins]]

Received June 5, 2007; revised version accepted October 24, 2007.

E-MAIL anton{at}med.unc.edu; FAX (919) 966-1844.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1580407

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