Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish

Henson, Hannah E.

doi:10.21007/etd.cghs.2014.0134

Cited by 5 publications

(9 citation statements)

References 173 publications

(367 reference statements)

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“…Similar to the ocular vasculature in mammalian embryos, zebrafish embryos possess choroidal and hyaloid networks that function similarly to their mammalian counterparts. 21,22 In order to better understand how the fzd4 mutation affects retinal vascularization, and to determine the time point at which fzd4 vasculature formation deviates from its control counterpart, we followed the developmental progression of the retinal vasculature in control and fzd4 fish for the first 12 weeks of development (n = 10 fish/genotype/week). We started our analysis at 1 week post-fertilization (wpf), as previous studies have methodically characterized the origin and formation of the ocular vasculature of zebrafish prior to this time point.…”

Section: Developmental Profiling Of Retinal Vasculature In Control supporting

confidence: 92%

Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina

Cáceres

Prykhozhij

Cairns

et al. 2019

Developmental Dynamics

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Background Familial exudative vitreoretinopathy (FEVR) is a rare congenital disorder characterized by a lack of blood vessel growth to the periphery of the retina with secondary fibrovascular proliferation at the vascular‐avascular junction. These structurally abnormal vessels cause leakage and hemorrhage, while the fibroproliferative scarring results in retinal dragging, detachment and blindness. Mutations in the FZD4 gene represent one of the most common causes of FEVR. Methods A loss of function mutation resulting from a 10‐nucleotide insertion into exon 1 of the zebrafish fzd4 gene was generated using transcription activator‐like effector nucleases (TALENs). Structural and functional integrity of the retinal vasculature was examined by fluorescent microscopy and optokinetic responses. Results Zebrafish retinal vasculature is asymmetrically distributed along the dorsoventral axis, with active vascular remodeling on the ventral surface of the retina throughout development. fzd4 mutants exhibit disorganized ventral retinal vasculature with discernable tubular fusion by week 8 of development. Furthermore, fzd4 mutants have impaired optokinetic responses requiring increased illumination. Conclusion We have generated a visually impaired zebrafish FEVR model exhibiting abnormal retinal vasculature. These fish provide a tractable system for studying vascular biology in retinovascular disorders, and demonstrate the feasibility of using zebrafish for evaluating future FEVR genes identified in humans.

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Section: Developmental Profiling Of Retinal Vasculature In Control supporting

confidence: 92%

Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina

Cáceres

Prykhozhij

Cairns

et al. 2019

Developmental Dynamics

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“…In addition to the BBB, the neural tissue is also protected by the blood-cerebrospinal fluid (CSF) barrier, which is created by the choroid plexus epithelial cells lining the brain ventricles (Wolburg and Paulus, 2010), and the arachnoid barrier, which is created by the epithelial cells beneath the dura that completely enwrap the brain (Abbott, 2004). These various brain barriers mature on different developmental timelines, with the blood-CSF barrier becoming impermeable by 4 dpf (Henson et al, 2014), then the BBB by 5 dpf (O’Brown et al, 2019), and the arachnoid barrier maturing after 9 dpf (Jeong et al, 2008) in zebrafish. While the focus of our study has been the BBB, it is possible that these additional brain barriers also play a role in the observed leakage of various tracers into the brain in spock1 mutants.…”

Section: Discussionmentioning

confidence: 99%

The secreted neuronal signal Spock1 regulates the blood-brain barrier

O'Brown

Patel

Hartmann

et al. 2021

Preprint

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The blood-brain barrier (BBB) is comprised of a single layer of endothelial cells with uniquely restrictive properties required for maintaining a tightly controlled homeostatic environment in the brain. Classic quail-chick grafting experiments showed that BBB properties are not intrinsic to brain endothelial cells, but instead are induced by signals from the embryonic brain microenvironment. Here we have identified a neuronally produced signal, Spock1, that specifically regulates BBB functional development in both zebrafish and mice without affecting angiogenesis. Using a combination of mosaic genetic analysis, tracer leakage assays and live imaging we show that Spock1 from neurons can regulate brain vasculature permeability non-cell autonomously. Electron microscopy analyses of spock1 mutants revealed that the leakage arises predominantly through increased endothelial transcytosis of both clathrin-independent small and large vesicles due to altered pericyte-endothelial interactions. Single-cell RNA sequencing analyses revealed a reduction in vascular expression of the cell adhesion molecule mcamb in the spock1 mutants, and this down-regulation of mcamb occurred specifically in regions with increased BBB leakage. These analyses indicate that the neuronal signal Spock1 regulates BBB properties by altering vascular gene expression and cellular interactions.

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“…We next sought to explore angiogenic cues responsible for vessel development in the fenestrated brain vascular beds, which is independent of Wnt/β-catenin signaling. Previous studies, including our recent work, characterized the vascularization processes of the mCP 12,15,17 , however, no angiogenic cues have (which was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Fenestrated Vascular Development At the Interface Of The Dcp...mentioning

confidence: 99%

Local angiogenic interplay of Vegfc/d and Vegfa drives brain region-specific development of fenestrated capillaries

Parab

Card

Chen

et al. 2022

Preprint

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Phenotypic diversity of brain vasculature is important for brain region-specific neural function, but how this diversity emerges remains unclear. Here we show a core angiogenic mechanism critical for fenestrated brain vessel development via a comparative analysis of the choroid plexuses (CPs) and circumventricular organs (CVOs) in zebrafish, demonstrating vessel-type-selective vascularization mechanisms. We find that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely-impaired brain angiogenesis without any apparent defect in fenestrated capillary formation in the CPs and CVOs. Conversely, various combinations of Vegfs direct heterogeneous regulation of angiogenesis within and across these organs. Expression analysis suggests that endothelial cells and non-neuronal cell types uniquely present in the CPs and CVOs are major sources of Vegfs. These comparative results reveal an unexpected, vital role for Vegfc in fenestrated vessel development across the brain and suggest that local and inter-tissue heterogeneity of angiogenic regulation promotes phenotypic diversity of brain vasculature.

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Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish

Cited by 5 publications

References 173 publications

Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina

Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina

The secreted neuronal signal Spock1 regulates the blood-brain barrier

Local angiogenic interplay of Vegfc/d and Vegfa drives brain region-specific development of fenestrated capillaries

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