BM88/Cend1 expression levels are critical for proliferation and differentiation of subventricular zone-derived neural precursor cells.
ABSTRACT Neural stem cells remain in two areas of the adult mammalian brain, the subventricular zone (SVZ) and the dentate gyrus of the hippocampus. Ongoing neurogenesis via the SVZ-rostral migratory stream pathway maintains neuronal replacement in the olfactory bulb (OB) throughout life. The mechanisms determining how neurogenesis is restricted to only a few regions in the adult, in contrast to its more widespread location during embryogenesis, largely depend on controlling the balance between precursor cell proliferation and differentiation. BM88/Cend1 is a neuronal lineage-specific regulator implicated in cell cycle exit and differentiation of precursor cells in the embryonic neural tube. Here we investigated its role in postnatal neurogenesis. Study of in vivo BM88/Cend1 distribution revealed that it is expressed in low levels in neuronal precursors of the adult SVZ and in high levels in postmitotic OB interneurons. To assess the functional significance of BM88/Cend1 in neuronal lineage progression postnatally, we challenged its expression levels by gain- and loss-of-function approaches using lentiviral gene transfer in SVZ-derived neurospheres. We found that BM88/Cend1 overexpression decreases proliferation and favors neuronal differentiation, whereas its downregulation using new-generation RNA interference vectors yields an opposite phenotype. Our results demonstrate that BM88/Cend1 participates in cell cycle control and neuronal differentiation mechanisms during neonatal SVZ neurogenesis and becomes crucial for the transition from neuroblasts to mature neurons when reaching high levels.
SourceAvailable from: Hisao Yamada01/2010; 62:7-12. DOI:10.5361/jkmu.62.7
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ABSTRACT: Purpose: BM88 is a cell cycle exit and neuronal differentiation protein that has been used as a marker of surviving RGCs after optic nerve injury. Thy1.1 has also been used as a marker for RGC loss but after optic nerve crush (ONC) a decrease in thy1 expression precedes the loss of RGCs. The purpose of this study was to determine if BM88 expression was correlated with RGC loss after ONC and optic nerve transection (ONT) injuries. Methods: Rats were injected with Fluorogold (FG) into the superior colliculus to label RGCs and received ONC or ONT 7 days later. Eyes were collected at 2-28 days after injury. Retinas were labeled with BM88 and intensity of the BM88 cell labeling was measured. Results: In control retinas, 98.9% of RGCs were immunoreactive (-IR) for BM88. There was a significant down regulation of BM88 by 52-80% of RGCs 7 days after ONC or ONT. The staining intensity of the remaining labeled cells was reduced to 41 - 51% of the control after 28 days of optic nerve injury. However, early in the injury there was a significant increase in the staining intensity of BM88. Conclusion: Nearly all BM88-IR RGCs co-localized with FG labeled RGCs in control retinas. However, both the number of BM88-IR RGCs and their intensity decreased gradually between 4 and 28 days, preceding the loss of FG labeled cells. These findings indicate that BM88 is not a good marker of surviving RGCs but may indicate abnormal RGC functioning, which precedes cell death.Investigative ophthalmology & visual science 02/2014; 55(3). DOI:10.1167/iovs.13-12986 · 3.66 Impact Factor
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ABSTRACT: In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.Science 05/2014; 344(6184). DOI:10.1126/science.1251141 · 31.48 Impact Factor