MRL/Faslpr mice is a lupus prone strain that exhibits lupus disease features at 12-16 weeks of age, including high-titer circulating anti-DNA antibodies, splenomegaly, lymphadnopathy, skin lesions, and IgG deposits in the kidney. At 16-24 weeks of age, CD4+ B220- CD44+ T cells were sorted into three populations based on the expression of two cell surface molecules, CD62L and PSGL1. CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo CD4+ T cells were isolated directly ex vivo. There was no treatment given to the animals. Naive (CD62Lhi CD44lo) CD4+ B220- T cells were isolated from young 6-8 week old female mice for comparison.
In vivo regulation of Bcl6 and T follicular helper cell development.
Specimen part
View SamplesThis work was designed to determine the role of the vascular endothelial growth factor A (VEGF) isoforms during early neuroepithelial development in the mammalian central nervous system (CNS), specifically in the forebrain. An emerging model of interdependence between neural and vascular systems includes VEGF, with its dual roles as a potent angiogenesis factor and neural regulator. Although a number of studies have implicated VEGF in CNS development, little is known about the role that the different VEGF isoforms play in early neurogenesis. We used a mouse model of disrupted VEGF isoform expression that eliminates the predominant brain isoform, VEGF164, and expresses only the diffusible form, VEGF120. We tested the hypothesis that VEGF164 plays a key role in controlling neural precursor populations in developing cortex. We used microarray analysis to compare gene expression differences between wild type and VEGF120 mice at E9.5, the primitive stem cell stage of the neuroepithelium. We quantified changes in PHH3-positive nuclei, neural stem cell markers (Pax6 and nestin) and the Tbr2-positive intermediate progenitors at E11.5 when the neural precursor population is expanding rapidly. Absence of VEGF164 (and VEGF188) leads to reduced proliferation without an apparent effect on the number of Tbr2-positive cells. There is a corresponding reduction in the number of mitotic spindles that are oriented parallel to the ventricular surface relative to those with a vertical or oblique angle. These results support a role for the VEGF isoforms in supporting the neural precursor population of the early neuroepithelium.
Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development.
Specimen part
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