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VEGF Isoform Transcriptome Changes in the E9.5 Murine Forebrain

ABSTRACT: Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice. Twelve E9.5 wildtype forebrain samples were compared to four E9.5 Vegf120 mouse forebrains, four E9.5 Vegf188 mouse forebrains, three E9.5 Vegf120/188 mouse forebrains, and four E11.5 wild type forebrains using the Mouse 430. 2.0 Affymetrix GeneChip. This study comprises of new samples and reanalysis of Samples from GSE30767 and GSE8091.

ORGANISM(S): Mus musculus

SUBMITTER: Jacob Cain

PROVIDER: E-GEOD-52542 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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VEGF Isoform Transcriptome Changes in the E9.5 Murine Forebrain

Project description:Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice.

2013-11-21 | GSE52542 | GEO

Mus musculus

Project description:VEGF Isoform Transcriptome Changes in the E9.5 Murine Forebrain

| PRJNA229418 | ENA

Expression data from rostral forebrains of wild-type and Fezf1-/- Fezf2-/- mice

Project description:Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon. We compared gene expression profiles of rostral forebrains, which contain the telencephalon and the rostral part of the diencephalon, from embryonic day (E) 9.5, E10.5, and E12.5 wild-type control and Fezf1-/- Fezf2 -/- mouse embryos. The forebrain rostral to the caudal limit of the lateral ventricles was isolated manually from E9.5, E10.5, and E12.5 wild-type and Fezf1-/- Fezf2-/- mice. Total RNAs were isolated by Separsol-RNA I and were used for microarray analyses.

2010-04-12 | E-GEOD-21156 | biostudies-arrayexpress

Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development

Project description:This 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. Four samples each of E9.5 wildtype or VEGF120 mouse forebrain were analyzed with the Mouse 430 2.0 Affymetrix GeneChip

2011-12-01 | E-GEOD-30767 | biostudies-arrayexpress

Prospective Identification, Isolation, and Profiling of a Telomerase-Expressing Subpopulation of Human Neural Stem Cells, using sox2 Enhancer-Directed Fluorescence-Activated Cell Sorting

Project description:Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors. We used adenoviral E/sox2:EGFP to transduce dissociates of the second trimester human ventricular zone (VZ)/ subventricular zone (SVZ), followed by EGFP-directed fluorescence-activated cell sorting (FACS). The sox2 isolates and unsorted controls from different gestational ages (16-19 wks, n=4) were then subject to RNA extraction and hybridization on Affymetrix microarrays.

2011-02-25 | E-GEOD-27505 | biostudies-arrayexpress

Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development

2011-12-01 | GSE30767 | GEO

Analysis of TBR1 downnstream target genes in embryonic forebrains

Project description:TBR1 is a forebrain specific T-box transcription factor. Tbr1-/- mice have been characterized by defective axonal projections from cerebral cortex and abnormal neuronal migration of cerebral cortex and amygdala. To investigate how TBR1 regulates neural development, the gene expression profile of Tbr1-/- brains was compared with WT littermates. Total RNAs purified from forebrains at embryonic day 16.5 were hybridized on Affymetrix microarrays

2013-12-31 | E-GEOD-49237 | biostudies-arrayexpress

Prospective Identification, Isolation, and Profiling of a Telomerase-Expressing Subpopulation of Human Neural Stem Cells, using sox2 Enhancer-Directed Fluorescence-Activated Cell Sorting

2011-02-25 | GSE27505 | GEO

Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

Project description:Through single cell transcriptome analysis, we uncovered molecular signatures of CD133+/GFAP- ependymal (E) cells, CD133+/GFAP+ neural stem (B) cells, Dlx2+ neuroblasts (A cells), and Sox10+ oligodendrocyte progenitors (O cells) in the adult mouse forebrain neurogenic zone. prominent hub genes of the gene network unique to ependymal CD133+/GFAP- quiescent cells are enriched for receptors of angiogenic factors and immune-responsive genes. Administration of VEGF activated CD133+ ependymal stem cells lining not only the lateral, but also the 4th ventricles, and together with bFGF, elicited subsequent neural lineage differentiation and migration. Examination of 28 single cells and 4 populations of 10 cells from adult mouse forebrain neurogenic zone.

2015-05-21 | E-GEOD-61288 | biostudies-arrayexpress

Life history shapes variation in egg composition in a wild passerine

Project description:Maternal investment directly shapes early developmental conditions and therefore has long-term fitness consequences for the offspring. In oviparous species prenatal maternal investment is fixed at the time of laying. To ensure the best survival chances for most of their offspring, females must equip their eggs with the resources required to perform well under various circumstances, yet the actual mechanisms remain unknown. Here we describe the blue tit egg albumen and yolk proteome and evaluate its potential to mediate maternal effects. We show that variation in egg composition (proteins, lipids, carotenoids) primarily depends on laying order, female age and paternity (within- versus extra-pair) and that the investment in the egg proteome is functionally biased among eggs. Our results suggest that maternal effects on egg composition result from both passive and active (partly compensatory) mechanisms, and that the between- and within-clutch variation in egg composition creates diverse biochemical environments for embryonic development.

2019-01-07 | PXD009822 | Pride

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