Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors

Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors
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DOI:
10.1523/jneurosci.2981-05.2005
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发表时间:
2005-11-30
影响因子:
5.3
通讯作者:
Gallo, V
Gallo, V
中科院分区:
医学1区
文献类型:
--
作者:
Aguirre, A;Rizvi, TA;Gallo, V

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细胞移植治疗脑损伤的成功方法包括选择合适的神经前体细胞类型和优化细胞植入的效率。在此,我们发现表皮生长因子受体(EGFR)的表达促进了出生后神经前体细胞在体外和体内的迁移。出生后脑室下带(SVZ)中的迁移NG2(+)祖细胞比非迁移的皮质NG2(+)细胞表达更高的EGFR水平。SVZ NG2(+)细胞内源性EGFR的高表达与其在体外和体内的迁移能力有关。通过瞬时转染法在皮质NG2(+)细胞中过表达EGFR,在体外和体内均将这些细胞转化为迁移表型。最后,从CNP启动子下过度表达EGFR的转基因小鼠中纯化的NG2(+)皮质细胞显示出增强的迁移能力。这些发现揭示了EGFR在出生后大脑中的新角色,并为优化脑组织修复的细胞植入开辟了新的途径。
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.