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. 2010. Published by Elsevier Ireland Ltd. All rights reserved.