The role of Brn-4 in the regulation of neural stem cell differentiation into neurons.
Brn-4, a member of the homeobox family of transcription factors, has previously been implicated in the regeneration and repair of denervated striatum. We investigated the effects of Brn-4 on the differentiation and development of neural stem cells (NSCs) from E16 rat hippocampus. Immunocytochemistry revealed that extracts of deafferented hippocampus promoted neuronal differentiation to a greater extent than extracts from normal hippocampus. Deafferented extracts also promoted maturation of newborn neurons as reflected in changes in cell areas and perimeters, and enhanced Brn-4 expression in MAP-2 positive neurons. Suppression or overexpression of Brn-4 in NSCs markedly decreased or increased neuronal differentiation and maturation of newborn neurons, respectively. These results suggest that Brn-4 expression is required both for neuronal differentiation of NSCs and maturation of newborn neurons, and that there may be some regulatory factors in deafferented hippocampus that can regulate Brn-4 expression in neuronal progenitors. Brn-4 is therefore a potential research target for the development of new therapeutics to promote brain repair.
Shi
Jinhong
J
Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, People's Republic of China.
Jin
Guohua
G
Zhu
Huixia
H
Tian
Meiling
M
Zhang
Xinhua
X
Qin
Jianbing
J
Tan
Xuefeng
X
D000344:Afferent Pathways; D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D050809:POU Domain Factors / Q000096:biosynthesis / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C484088:Pou3f4 protein, rat; D014020:Tissue Extracts