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The Journal of Neuroscience, November 30, 2005, 25(48):11092-11106; doi:10.1523/JNEUROSCI.2981-05.2005

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Development/Plasticity/Repair
Overexpression of the Epidermal Growth Factor Receptor Confers Migratory Properties to Nonmigratory Postnatal Neural Progenitors

Adan Aguirre,¹ Tilat A. Rizvi,² Nancy Ratner,² and Vittorio Gallo¹

¹Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, and ²Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229

Approaches to successful cell transplantation therapies for the injured brain involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment. Here we show that epidermal growth factor receptor (EGFR) expression enhances postnatal neural progenitor migration in vitro and in vivo. Migratory NG2-expressing (NG2⁺) progenitor cells of the postnatal subventricular zone (SVZ) express higher EGFR levels than nonmigratory, cortical NG2⁺ cells. The higher endogenous EGFR expression in SVZ NG2⁺ cells is causally related with their migratory potential in vitro as well as in vivo after cell engraftment. EGFR overexpression in cortical NG2⁺ cells by transient transfection converted these cells to a migratory phenotype in vitro and in vivo. Finally, cortical NG2⁺ cells purified from a transgenic mouse in which the EGFR is overexpressed under the CNP promoter exhibited enhanced migratory capability. These findings reveal a new role for EGFR in the postnatal brain and open new avenues to optimize cell engraftment for brain repair.

Key words: CNP-EGFP mouse; cell transplantation; cell migration; rostral migratory stream; white matter; hippocampus; olfactory bulb

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Received July 19, 2005; revised October 12, 2005; accepted October 16, 2005.

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