VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish

Jensen, Lasse D.; Nakamura, Masaki; Bräutigam, Lars; Li, Xuri; Liu, Yizhi; Samani, Nilesh J.; Cao, Yihai

doi:10.1073/pnas.1510245112

Cited by 37 publications

(27 citation statements)

References 44 publications

(62 reference statements)

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“…Intriguingly, the vascular disruption observed in znf408 mutants seemed to be specific to the hyaloid/retinal vasculature. This is in line with other studies demonstrating specific requirements for PI3K, 30 VEGF-B, 31 or vitamin D 32 in the development of the hyaloid vessels in zebrafish. The specific role of these signaling pathways and whether they constitute different points in the same pathway or contribute to several independent pathways that converge on regulating retinal vascular development is an area of future investigation.…”

Section: Discussionsupporting

confidence: 92%

Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature

Karjosukarso

Ali

Peters

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease in which the retinal vasculature is affected. Patients with FEVR typically lack or have abnormal vasculature in the peripheral retina, the outcome of which can range from mild visual impairment to complete blindness. A missense mutation (p.His455Tyr) in ZNF408 was identified in an autosomal dominant FEVR family. Little, however, is known about the molecular role of ZNF408 and how its defect leads to the clinical features of FEVR. METHODS. Using CRISPR/Cas9 technology, two homozygous mutant zebrafish models with truncated znf408 were generated, as well as one heterozygous and one homozygous missense znf408 model in which the human p.His455Tyr mutation is mimicked. RESULTS. Intriguingly, all three znf408-mutant zebrafish strains demonstrated progressive retinal vascular pathology, initially characterized by a deficient hyaloid vessel development at 5 days postfertilization (dpf) leading to vascular insufficiency in the retina. The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf. CONCLUSIONS. Together, our data demonstrate an important role for znf408 in the development and maintenance of the vascular system within the retina.

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Section: Discussionsupporting

confidence: 92%

Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature

Karjosukarso

Ali

Peters

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Mirroring previous reports of vegfaa expression, vegfaa:EGFP fish displayed EGFP fluorescence in developing somites, indicating that vegfaa regulatory sequences faithfully report domains of endogenous vegfaa (SI Appendix, Fig. S1 A and B) (20)(21)(22)(23)(24). During cardiac development, the expression domain for Vegfa varies among…”

Section: Resultssupporting

confidence: 62%

Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish

Karra

Foglia

Choi

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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During heart development and regeneration, coronary vascularization is tightly coupled with cardiac growth. Although inhibiting vascularization causes defects in the innate regenerative response of zebrafish to heart injury, angiogenic signals are not known to be sufficient for triggering regeneration events. Here, by using a transgenic reporter strain, we found that regulatory sequences of the angiogenic factor are active in epicardial cells of uninjured animals, as well as in epicardial and endocardial tissue adjacent to regenerating muscle upon injury. Additionally, we find that induced cardiac overexpression of in zebrafish results in overt hyperplastic thickening of the myocardial wall, accompanied by indicators of angiogenesis, epithelial-to-mesenchymal transition, and cardiomyocyte regeneration programs. Unexpectedly, overexpression in the context of cardiac injury enabled ectopic cardiomyogenesis but inhibited regeneration at the site of the injury. Our findings identify Vegfa as one of a select few known factors sufficient to activate adult cardiomyogenesis, while also illustrating how instructive factors for heart regeneration require spatiotemporal control for efficacy.

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“…Angiogenesis inhibitors now constitute a clinical anticancer strategy . Vascular endothelial growth factor is considered a key mediator of angiogenesis and a promising therapeutic target in cancer . Our results showed that Notch4 silencing downregulated the expression of VEGF.…”

Section: Discussionmentioning

confidence: 58%

Notch4+ cancer stem‐like cells promote the metastatic and invasive ability of melanoma

et al. 2016

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Sphere formation in conditioned serum‐free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor (tumorospheres) is considered useful for the enrichment of cancer stem‐like cells, also known as tumor‐initiating cells. We used a gene expression microarray to investigate the gene expression profile of melanoma cancer stem‐like cells (MCSLCs). The results showed that MCSLCs highly expressed the following Notch signaling pathway molecules: Notch3 (NM_008716), Notch4 (NM_010929), Dtx4 (NM_172442), and JAG2 (NM_010588). Immunofluorescence staining showed tumorosphere cells highly expressed Notch4. Notch4high B16F10 cells were isolated by FACS, and Western blotting showed that high Notch4 expression is related to the expression of epithelial–mesenchymal transition (EMT)‐associated proteins. Reduced invasive and migratory properties concomitant with the downregulation of the EMT markers Twist1, vimentin, and VE‐cadherin and the overexpression of E‐cadherin was observed in human melanoma A375 and MUM‐2B cells. In these cells, Notch4 was also downregulated, both by Notch4 gene knockdown and by application of the γ‐secretase inhibitor, DAPT. Mechanistically, the re‐overexpression of Twist1 by the transfection of cells with a Twist1 expression plasmid led to an increase in VE‐cadherin expression and a decrease in E‐cadherin expression. Immunohistochemical analysis of 120 human melanoma tissues revealed a significant correlation between the high expression of Notch4 and the metastasis of melanoma. Taken together, our findings indicate that Notch4+ MCSLCs trigger EMT and promote the metastasis of melanoma cells.

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VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish

Cited by 37 publications

References 44 publications

Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature

Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature

Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish

Notch4+ cancer stem‐like cells promote the metastatic and invasive ability of melanoma

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