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.
Tan
Xue-Feng
XF
Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China.
Qin
Jian-Bing
JB
Jin
Guo-Hua
GH
Tian
Mei-Ling
ML
Li
Hao-Ming
HM
Zhu
Hui-Xia
HX
Zhang
Xin-Hua
XH
Shi
Jin-Hong
JH
Huang
Zhen
Z
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