Effects of Brn-4 on the neuronal differentiation of neural stem cells derived from rat midbrain.
NSCs (neural stem cells) provide a powerful research tool for the design and discovery of new approaches to cell replacement therapy during brain repair. However, the usefulness of this tool has been particularly obstructed by limited neuronal differentiation of NSCs. Brn-4, a member of the POU domain family of transcription factors, has been previously implicated in the development of neurons by expression analysis. Here, we directly investigated the effects of Brn-4 on the neuronal differentiation and development of NSCs derived from the E13 rat midbrain. We found that Brn-4 knockdown in NSCs resulted in a significant decrease of MAP-2-positive neurons with immature morphology. Overexpression of Brn-4 in NSCs markedly increased the production and maturation of newborn neurons. These results suggest that Brn-4 has a critical role in the neuronal differentiation of mesencephalic NSCs and the maturation of newborn neurons. Brn-4 may be utilized to manipulate NSCs for gene and cell therapy of several neurological diseases.
Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China.
Xue-Feng
XF
Tan
Jian-Bing
JB
Qin
Guo-Hua
GH
Jin
Mei-Ling
ML
Tian
Hao-Ming
HM
Li
Hui-Xia
HX
Zhu
Xin-Hua
XH
Zhang
Jin-Hong
JH
Shi
Zhen
Z
Huang
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002999:Clone Cells; D005455:Fluorescent Antibody Technique; D008164:Luminescent Proteins / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D050809:POU Domain Factors / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection
D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C484088:Pou3f4 protein, rat; D011994:Recombinant Proteins; C413663:fluorescent protein 583