Robo4

Weitzman, Matthew D.; Bayley, Edward B.; Naik, Ulhas P.

doi:10.4161/cam.2.4.7061

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Importantly, a functionally relevant interaction between Slit2 and Robo4 does not preclude Slit2 or Robo4 from interacting with alternate partners, such as Robo1-3 or Unc5b. 46,47,53,59 We confirmed that radiation is harmful to all cells within the BM compartment, including stromal populations (Fig. 2).…”

Section: Methodssupporting

confidence: 64%

“…40,52 OBC-expressed Slit2, therefore, has two likely cellular targets within the BM, HSC and EC. Slit2 has previously been reported to elicit both attractant and repellant effects on endothelial cells in vitro 42,[52][53][54][55][56][57][58] and to stabilize the vascular endothelium in vivo by a Robo4-dependent mechanism, [41][42][43] while Slit2's effects on HSC are less explored. Interestingly, neither deletion of Robo4 nor exposure of wt HSC to Slit2 led to detectable proliferative or migratory responses in vitro.…”

Section: Methodsmentioning

confidence: 99%

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Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations

Smith-Berdan¹,

Schepers²,

Ly³

et al. 2012

Cell Cycle

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The bone marrow (BM) niche is essential for lifelong hematopoietic stem cell (HSC) maintenance, proliferation and differentiation. Several BM cell types, including osteoblast lineage cells (OBC), mesenchymal stem cells (MSC) and endothelial cells (EC) have been implicated in supporting HSC location and function, but the relative importance of these cell types and their secreted ligands remain controversial. We recently found that the cell surface receptors Robo4 and CXCR4 cooperate to localize HSC to BM niches. We hypothesized that Slit2, a putative ligand for Robo4, cooperates with the CXCR4 ligand SDF1 to direct HSC to specific BM niche sites. Here, we have isolated OBC, MSC and EC by flow cytometry and determined their frequency within the bone marrow and the relative mRNA levels of Slit2, SDF1 and Robo4. We found that expression of Slit2 and SDF1 were dynamically regulated in MSC and OBC-like populations following radiation, while Robo4 expression was restricted to EC. Radiation also significantly affected the cellularity and frequency of both the non-adherent and adherent cells within the BM stroma. These data support a physiological role for Slit2 in regulating the dynamic function of Robo-expressing cells within BM niches at steady state and following radiation.

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Section: Methodssupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations

Smith-Berdan¹,

Schepers²,

Ly³

et al. 2012

Cell Cycle

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“…Nrp-1 is a VEGF-A coreceptor that forms an ectodomain complex with VEGFR2 that regulates the permeabilizing effects of VEGF [ 127 , 142 , 144 , 145 ], and Nrp-1 binding to VEGFR2 is further regulated by the binding of semaphorin3A (sema3A) [ 145 – 147 ]. Endothelial roundabout receptors, Robo1 and Robo4, also impact VEGFR2-directed permeability through discrete signaling pathways [ 36 , 48 , 148 – 150 ]. Slit-2 binding to Robo1 and Robo4, respectively, have positive or negative effects on VEGF-A directed EC permeability [ 151 , 152 ].…”

Section: Unique Receptors Regulate Ec Permeabilitymentioning

confidence: 99%

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

Gavrilovskaya

Gorbunova

Matthys

et al. 2012

Advances in Virology

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American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

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“…Vertebrates express three Slits [25,30-33] and four Robos : Robo1 , Robo2 , and Robo3/Rig1 are expressed in the developing nervous system [34,35]. Robo4 (Magic Roundabout) differs markedly in its domain structure from the other Robos and is expressed exclusively in endothelial cells [36,37]. A role for Robo4 in angiogenesis has been described in mice [38] and zebrafish [39].…”

Section: Introductionmentioning

confidence: 99%

RabGDI controls axonal midline crossing by regulating Robo1 surface expression

et al. 2012

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BackgroundAxons navigate to their future synaptic targets with the help of choice points, intermediate targets that express axon guidance cues. Once they reach a choice point, axons need to switch their response from attraction to repulsion in order to move on with the next stage of their journey. The mechanisms underlying the change in axonal responsiveness are poorly understood. Commissural axons become sensitive to the repulsive activity of Slits when they cross the ventral midline of the CNS. Responsiveness to Slits depends on surface expression of Robo receptors. In Drosophila, Commissureless (Comm) plays a crucial regulatory role in midline crossing by keeping Robo levels low on precommissural axons. Interestingly, to date no vertebrate homolog of comm has been identified. Robo3/Rig1 has been shown to control Slit sensitivity before the midline, but without affecting Robo1 surface expression.ResultsWe had identified RabGDI, a gene linked to human mental retardation and an essential component of the vesicle fusion machinery, in a screen for differentially expressed floor-plate genes. Downregulation of RabGDI by in ovo RNAi caused commissural axons to stall in the floor plate, phenocopying the effect observed after downregulation of Robo1. Conversely, premature expression of RabGDI prevented commissural axons from entering the floor plate. Furthermore, RabGDI triggered Robo1 surface expression in cultured commissural neurons. Taken together, our results identify RabGDI as a component of the switching mechanism that is required for commissural axons to change their response from attraction to repulsion at the intermediate target.ConclusionRabGDI takes over the functional role of fly Comm by regulating the surface expression of Robo1 on commissural axons in vertebrates. This in turn allows commissural axons to switch from attraction to repulsion at the midline of the spinal cord.

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Robo4

Cited by 6 publications

References 11 publications

Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations

Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

RabGDI controls axonal midline crossing by regulating Robo1 surface expression

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