| With the lucubrating studies on neural stem cells (NSCs), the anterior subventricular zone (SVZa) as a special area where NSCs are concentrated has been focused by more and more reseachers. NSCs derived from SVZa not only possess the characteristics of NSCs, but also have their own features: 1) they will migrate form SVZa to olfactory bulb (OB) along an especial routeway- the rostral migratory stream (RMS) after they are produced; 2) they will maintain proliferating and the characters of neural progenitor; 3) they differentiate into maturated neurons while migrating to destination and become the renewing resource of OB interneurons in the whole life of mammal animals, which is the unique character of SVZa NSCs differed from other NSCs. However, the development of SVZa NSCs are affected not only by inherit genes, but also by the extracellular signals. Recently, there were increasing evidences that many extracellular signals regulate the proliferation and differentiation of NSCs, such as mitogenic factors (EGF), transcription factors (BMPs, Mash1, Pax6, and Wnt) and so on. Increasing evidences suggested that the fate of neural progenitors is regulated by members of BMPs. BMPs belong to transforming growth factor-β (TGF-β) superfamily, which were originally identified and characterized by their novel ability to induce cartilage and bone formation in ectopic extraskeletal site in vivo. Recently, several members of this family have been isolated, cloned, and expressed as recombinant protein in mammals, include BMP-2, BMP-3, BMP-4 and BMP-5 and so on. BMPs exert their cellular effects by binding to transmembrane receptors that possess serine/threonine kinase activities. Following ligand activation, the receptor kinase phosphorylates Smads family, then, they form functional compounds that move into the nucleus to stimulate the transcription of target genes.Accumulating evidences indicated that BMP-2 has an important role in the development of nervous system (NS), especially in the differentiation, maturation and apoptosis of neural stem cells. Expressions of BMP-2 and BMPRs in the developing nervous system suggested that BMP-2 could affect proliferation and differentiation of NSCs. At the same time, some evidences indicated that BMP-2 could induce NSCs differentiating into neurons depending on the concentration. Moreover, it was considered that BMP-2 regulates the differentiation of NSCs through Smad signaling pathways (described above). Nevertheless, the effects of BMP-2 on the SVZa NSCs differentiation have not been clearly studied while they migrate from SVZa into OB through RMS. Although there were reports that rhBMP-2 can efficiently induce neuronal differentiation of SVZa NSCs in vitro, the precise mechanism of it is still unknown.In our study, we first investigated the expressions of BMP-2 mRNA in SVZa-RMS-OB of rat brain at different developing phases by RT-PCR, then observed the temporal and spatial expression patterns of BMP-2 in SVZa-RMS-OB by immunofluorescent staining of BMP-2, nestin, NF200 and GFAP. The results are as follows: 1. NSCs derived from SVZa migrate from SVZa into OB through RMS in developing rat brain; the expressions of nestin are located manly in the SVZa and its surrounding, the RMS and the center of OB, but nestin positive cells are gradually decreased with the development of rat brain. 2. The expressions of NF and GFAP were low level in SVZa-RMS-OB, their expressions were located around of LV and SVZa, OB, there were almost no expressed NF and GFAP in RMS, but the expressions of NF and GFAP were high around OB. The expressions of NF and GFAP have an increasing trend with the development phrase. 3. The expressions of BMP-2: ①in different time points: The expressions of BMP-2 were higher in embryonic day 14 (E14) than that of postnatal day 0 (P0), postnatal day 7 (P7) and adult in the locations of SVZa, RMS and OB, and there were not significant differences between P0 and P7. The expressions of BMP-2 are lowest in adult. ②in different locations: The expressions of BMP-2... |
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