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GSE30767
Mus musculus
1 Downloadable Sample
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.
Publication Title
Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 42 Downloadable Samples
Description
The assembly of neural circuits involves multiple sequential steps such as the specification of cell types, their migration to proper brain locations, morphological and physiological differentiation, and the formation and maturation of synaptic connections. This intricate and often prolonged process is guided by elaborate genetic mechanisms that regulate each developmental event. Evidence from numerous systems suggests that each cell type, once specified, is endowed with a genetic program that directs its subsequent development. This cell intrinsic program unfolds in respond to, and is regulated by, extrinsic signals, including cell-cell and synaptic interactions. To a large extent, the execution of this genetic program is achieved by the expression of specific sets of genes that support distinct developmental processes. Therefore, a comprehensive analysis of the developmental progression of gene expression in synaptic partners of neurons may provide a basis for exploring the genetic mechanisms regulating circuit assembly.
Publication Title
Developmental Coordination of Gene Expression between Synaptic Partners During GABAergic Circuit Assembly in Cerebellar Cortex.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 1 Downloadable Sample
Description
Zebrafish is ideal model organism to study myelination and demyelination. We could use this model to screen demylination relative genes and provide a new idea for clinic therapy.
Publication Title
Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous system demyelination.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
ES cells differentiated in the presence of the Wnt inhibitor DKK1 fail to express the transcription factor Snail and undergo EMT. We generated an ES cell line, A2.snail, that induced Snail expression upon addition of doxycycline addition.
Publication Title
Snail and the microRNA-200 family act in opposition to regulate epithelial-to-mesenchymal transition and germ layer fate restriction in differentiating ESCs.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 41 Downloadable Samples
Description
Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin 8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
Publication Title
Identification of a gene regulatory network associated with prion replication.
Sample Metadata Fields
Treatment
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