Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors.
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.
Aguirre
Adan
A
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
Rizvi
Tilat A
TA
Ratner
Nancy
N
Gallo
Vittorio
V
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000941:Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001921:Brain / Q000166:cytology; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology; D002552:Cerebral Ventricles; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D010641:Phenotype; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016326:Extracellular Matrix Proteins; D020098:Natriuretic Peptide, C-Type; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4