Assessment of Vascular Patterning in the Zebrafish

Stratman, Amber N.; Weinstein, Brant M.

doi:10.1007/978-1-0716-0916-3_15

Cited by 6 publications

(5 citation statements)

References 62 publications

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“…Published transgenic fish lines used in experiments include Tg ( gata1 : DsRed ) sd2Tg 48 , Tg(kdrl:EGFP) s8 43 49 , Tg(fli:EGFP) y1 50 , and Tg(egfl7:GAL4FF) gSAlzGFFD478A 51, 52 .…”

Section: Methodsmentioning

confidence: 99%

Section: Studies Of Human Patients and Disease Models With Cerebral Cavernous Malformations (Ccms)mentioning

confidence: 99%

“…Embryos develop externally, making them highly amenable to genetic manipulation. Optical transparency and transgenic strains permit visualization of hemorrhage and vascular development in vivo , in real-time through time-lapse microscopy 42, 43 . The small size of zebrafish embryos allows them to survive and continue their development for many days in the absence of circulatory function, facilitating assessment of the specificity of vascular defects.…”

Section: Introductionmentioning

confidence: 99%

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In vivodissection of Rhoa function in vascular development using zebrafish

et al. 2021

Preprint

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Rationale: The small monomeric GTPase RHOA acts as a master regulator of signal transduction cascades by activating effectors of cellular signaling, including the Rho-associated protein kinases ROCK1/2. Previous in vitro cell culture studies suggest that RHOA can regulate many critical aspects of vascular endothelial cell (EC) biology, including focal adhesion, stress fiber formation, and angiogenesis. However, the specific in vivo roles of RHOA during vascular development and homeostasis are still not well understood. Objective: In this study we examine the in vivo functions of RHOA in regulating vascular development and integrity in zebrafish. Methods and Results: We use zebrafish RHOA-ortholog (rhoaa) mutants, transgenic embryos expressing wild type, dominant-negative, or constitutively active forms of rhoaa in ECs, and a pharmacologic inhibitor of ROCK1/2 to study the in vivo consequences of RHOA gain- and loss-of-function in the vascular endothelium. Our findings document roles for RHOA in vascular integrity, developmental angiogenesis, and vascular morphogenesis. Conclusions: Our results indicate that either too much or too little RHOA activity leads to vascular dysfunction in vivo.

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“…Published transgenic fish lines used in experiments include Tg ( gata1 : DsRed ) sd2Tg 48 , Tg(kdrl:EGFP) s8 43 49 , Tg(fli:EGFP) y1 50 , and Tg(egfl7:GAL4FF) gSAlzGFFD478A 51, 52 .…”

Section: Methodsmentioning

confidence: 99%

Section: Studies Of Human Patients and Disease Models With Cerebral Cavernous Malformations (Ccms)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivodissection of Rhoa function in vascular development using zebrafish

et al. 2021

Preprint

Self Cite

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“…VSMC differentiation is difficult to observe in vivo with mammalian models, as mammalian embryos develop in utero and depend on maternal circulation. Zebrafish is an important vertebrate model for vascular development, as zebrafish embryos are externally fertilized, optically clear, and thus accessible to confocal live imaging of developing blood vessels ( Stratman and Weinstein, 2021 ). Establishment of zebrafish fluorescent transgenic reporter lines with pdgfrb and acta2 promoters enables in vivo visualization and assessment of mural cells and VSMCs ( Ando et al, 2016 ; Whitesell et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis

Cheng,

Xia,

Wanner

et al. 2024

eLife

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Brain arteries are wrapped by vascular smooth muscle cells (VSMCs). Fully differentiated VSMCs are important for brain artery homeostasis, and they are lost in several cerebrovascular diseases. How healthy VSMCs differentiate on different brain arteries during development is unclear. Such knowledge will help regenerate lost VSMCs in brain arteriopathy. To answer this question, we studied the developmental muscularization of the zebrafish circle of Willis (CW) arteries, the major arterial loop that supplies blood to the brain in all vertebrates. We found that artery specification of CW endothelial cells (ECs) happens after they migrate from primitive veins to form CW arteries. VSMCs differentiate from pdgfrb+ common vascular mural cell progenitors at the time when embryo circulation starts and progress temporally and spatially from anterior to posterior CW arteries. Computational fluid dynamic simulation confirms that earlier VSMC differentiation coincide with higher pulsatile flow hemodynamics in anterior CW arteries. Pulsatile blood flow induces the differentiation of human brain pdgfrb+ progenitors into VSMCs and reducing pulsatile blood flow by blocking the zebrafish embryo heartbeat after pdgfrb+ recruitment but before VSMC differentiation limits the number of mature VSMCs. Congruently, the flow responsive transcription factor klf2a is activated in ECs before VSMC differentiation and knockdown delays VSMC differentiation on CW arteries. Overall, our data place hemodynamic activation of endothelial klf2a signaling as key determinant of spatiotemporal VSMC differentiation on CW arteries.

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“…VSMC differentiation is difficult to observe in vivo with mammalian models, as mammalian embryos develop in utero and depend on maternal circulation. Zebrafish is an important vertebrate model for vascular development, as zebrafish embryos are externally fertilized, optically clear, and thus accessible to confocal live imaging of developing blood vessels (Stratman & Weinstein, 2021). Establishment of zebrafish fluorescent transgenic reporter lines with pdgfrb and acta2 promoters enables in vivo visualization and assessment of mural cells and VSMCs (Ando et al, 2016; Whitesell et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis

Cheng,

Xia,

Wanner

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Brain arteries are wrapped by vascular smooth muscle cells (VSMCs). Fully differentiated VSMCs are important for brain artery homeostasis, and they are lost in several cerebrovascular diseases. How healthy VSMCs differentiate on different brain arteries during development is unclear. Such knowledge will help regenerate lost VSMCs in brain arteriopathy. To answer this question, we studied the developmental muscularization of the zebrafish circle of Willis (CW) arteries, the major arterial loop that supplies blood to the brain in all vertebrates. We found that artery specification of CW endothelial cells (ECs) happens after they migrate from primitive veins to form CW arteries. VSMCs differentiate frompdgfrb+common vascular mural cell progenitors at the time when embryo circulation starts and progress temporally and spatially from anterior to posterior CW arteries. Computational fluid dynamic simulation confirms that earlier VSMC differentiation coincide with higher pulsatile flow hemodynamics in anterior CW arteries. Pulsatile blood flow induces the differentiation of human brainpdgfrb+progenitors into VSMCs and reducing pulsatile blood flow by blocking the zebrafish embryo heartbeat afterpdgfrb+recruitment but before VSMC differentiation limits the number of mature VSMCs. Congruently, the flow responsive transcription factorklf2ais activated in ECs before VSMC differentiation and knockdown delays VSMC differentiation on CW arteries. Overall, our data place hemodynamic activation of endothelialklf2asignaling as key determinant of spatiotemporal VSMC differentiation on CW arteries.

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Assessment of Vascular Patterning in the Zebrafish

Cited by 6 publications

References 62 publications

In vivodissection of Rhoa function in vascular development using zebrafish

In vivodissection of Rhoa function in vascular development using zebrafish

Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis

Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis

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