Developmental regulation of long-range neuroblast migration by Eph/ephrin signaling
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ABSTRACT:
PROVIDER: PRJNA1312064 | ENA |
REPOSITORIES: ENA
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Project description:In the developing mouse anterior forebrain, the rostral migratory stream (RMS) supports continued proliferation and efficient transportation of large quantities of neuroblasts from the ventricular-subventricular (V-SVZ) stem cell niche to the olfactory bulb (OB). Astrocytes aid this migration by providing a glial network through which chains of fasciculated neuroblasts move. The largest receptor tyrosine kinase family, Eph receptors, and their ephrin ligands have been implicated in controlling neuroblast migration and astrocyte organization within this pathway. However, a clear understanding of the regulatory mechanisms underlying Eph/ephrin signaling remains elusive, in part due to the complexity of heterogeneous expression patterns in both neuroblasts and astrocytes, as well as the cytoarchitectural changes that occur during postnatal development. Our studies provide a framework to deconvolute and characterize Eph and ephrin signaling as the RMS changes from a diffuse stream of migratory neuroblasts to a highly constricted pathway of neuroblast chains within astrocytic networks. Specifically, we identify temporally regulated, cell type-specific receptor-ligand interactions, revealing the prevalence and dynamic shifts of neuroblast-neuroblast, neuroblast-astrocyte, astrocyte-astrocyte interactions.
2025-09-04 | GSE306762 | GEO
Project description:The hypothesis tested in the present study was that activation of Eph or ephrin signaling in neural progenitors induces a transcriptional response which participate in the control of progenitor self-renewal. Results provide important information on transcriptional changes in response to activation of Eph receptors. They also show that activation of ephrin signaling does not induce a transcriptional response at genome-wide level.
2017-09-21 | GSE104068 | GEO
Project description:Cell-specific information processing in segregating populations of Eph receptor-ephrin-expressing cells
2009-12-11 | PRD000814 | Pride
Project description:Cell segregation allows the compartmentalization of cells with similar fates during morphogenesis, which can be enhanced by cell fate plasticity in response to local molecular and biomechanical cues. Endothelial tip cells in the growing retina, which lead vessel sprouts, give rise to arterial endothelial cells and thereby mediate arterial growth. Here, we have combined cell type-specific and inducible mouse genetics, flow experiments in vitro, single cell RNA sequencing and biochemistry to show that the balance between ephrin-B2 and its receptor EphB4 is critical for arterial specification, cell sorting and arteriovenous patterning. At the molecular level, elevated ephrin-B2 function after loss of EphB4 enhances signaling responses by the Notch pathway, VEGF and the transcription factor Dach1, which is influenced by endothelial shear stress. Our findings reveal how Eph-ephrin interactions integrate cell segregation and arteriovenous specification in the vasculature, which has potential relevance for human vascular malformations caused by EPHB4 mutations.
2024-01-30 | GSE223738 | GEO
Project description:Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1+ GC B cells increases during the course of an immune response with Ephrin-B1+ GC B cells displaying elevated levels of Bcl6, S1pr2, and Aicda relative to their Ephrin-B1– counterparts. We further identified a small proportion of recently dividing, somatically mutated Ephrin-B1+ GC B cells that have begun to downregulate Bcl6 and S1pr2 and express markers associated with memory B cells such as CD38 and EBI2. Transcriptional analysis indicates that these cells are developmentally related to memory B cells, and likely represent a population of GC memory precursor (PreMem) B cells. GC PreMem cells display enhanced survival relative to bulk GC B cells, localize near the edge of the GC and are predominantly found within the light zone. These findings offer insight into the significant heterogeneity that exists within the GC B cell population and provide tools to further dissect signals regulating the differentiation of GC B cells.
2017-01-26 | GSE89897 | GEO
Project description:Eph-ephrin signaling couples endothelial cell sorting and arterial specification
| PRJNA928081 | ENA
Project description:Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and also functions as a cell entry receptor for several henipaviruses, which are zoonotic viruses with pandemic potential. Two such viruses, Nipah (NiV) and Hendra (HeV), are highly pathogenic in humans yet do not have any widely approved virus-specific therapeutics or vaccines. Soluble Fc-fusions of EFNB2 (sEFNB2-Fc) are known to bind the attachment glycoprotein G of both viruses and inhibit viral infection of cells. However, the potential of sEFNB2-Fc as a neutralizing agent in vivo is hindered by its binding activity to native Eph receptors. Therefore, using deep mutagenesis, variants of EFNB2 at cell surface are identified with increased binding to the soluble head domain of NiV-G over soluble Fc-fusions of the extracellular domains of Eph receptors. Specificity mutations for NiV-G are found primarily at the binding interface, especially around the G-H binding loop. The mutational landscape offers a preliminary blueprint for engineering sEFNB2-Fc variants with high specificity and affinity for potent neutralization of henipaviruses.
2023-06-12 | GSE234213 | GEO
Project description:Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and also functions as a cell entry receptor for several henipaviruses, which are zoonotic viruses with pandemic potential. Two such viruses, Nipah (NiV) and Hendra (HeV), are highly pathogenic in humans yet do not have any widely approved virus-specific therapeutics or vaccines. Soluble Fc-fusions of EFNB2 (sEFNB2-Fc) are known to bind the attachment glycoprotein G of both viruses and inhibit viral infection of cells. However, the potential of sEFNB2-Fc as a neutralizing agent in vivo is hindered by its binding activity to native Eph receptors. Therefore, using deep mutagenesis, variants of EFNB2 at cell surface are identified with increased binding to the soluble head domain of NiV-G over soluble Fc-fusions of the extracellular domains of Eph receptors. Specificity mutations for NiV-G are found primarily at the binding interface, especially around the G-H binding loop. The mutational landscape offers a preliminary blueprint for engineering sEFNB2-Fc variants with high specificity and affinity for potent neutralization of henipaviruses.
2023-06-12 | GSE234214 | GEO
Project description:The goal of this study was to identify immediate early transcriptional targets of ephrin-B1 forward signaling that are relevant to palatogenesis. The Ephs compose a family of receptor tyrosine kinase signaling molecules that can be activated by their cognate ligands, the ephrins. Despite the importance of Eph/ephrin signaling in a wide variety of developmental and cell biological processes, a potential downstream transcriptional response has not been explored. To understand the role of ephrin-B1 signaling in palatogenesis, we examined transcriptional response to ephrin-B1 in a primary mouse embryonic palatal shelf cell culture system. We find an immediate early signature of gene expression that reflects the activation of Erk/MAPK signaling by ephrin-B1 signaling in the palatal shelves. Induction of primary palate cells with 2 ug/ml of pre-clustered ephrin-B1 for one hour. Uninduced primary palate cells are the control. Four replicates each.
2010-09-20 | E-GEOD-23539 | biostudies-arrayexpress
Project description:The goal of this study was to identify immediate early transcriptional targets of ephrin-B1 forward signaling that are relevant to palatogenesis. The Ephs compose a family of receptor tyrosine kinase signaling molecules that can be activated by their cognate ligands, the ephrins. Despite the importance of Eph/ephrin signaling in a wide variety of developmental and cell biological processes, a potential downstream transcriptional response has not been explored. To understand the role of ephrin-B1 signaling in palatogenesis, we examined transcriptional response to ephrin-B1 in a primary mouse embryonic palatal shelf cell culture system. We find an immediate early signature of gene expression that reflects the activation of Erk/MAPK signaling by ephrin-B1 signaling in the palatal shelves.
2010-09-21 | GSE23539 | GEO