The effect of absent blood flow on the zebrafish cerebral and trunk vasculature

Kugler, Elisabeth; Snodgrass, Ryan; Bowley, George; Plant, Karen; Serbanovic-Canic, Jovana; Hamilton, Noémie; Evans, Paul C.; Chico, Timothy J. A.; Armitage, Paul A.

doi:10.1530/vb-21-0009

Cited by 13 publications

(6 citation statements)

References 79 publications

(137 reference statements)

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“…Loss of tnnt2a gives rise to a "silent heart phenotype" lacking cardiac contractions and blood flow, along with impaired venous angiogenesis and absence of a CVP. 20 Injection of ≈2 ng of tnnt2a MO resulted in complete inhibition of CVP formation as early as 28 hpf, with no apparent effects on ventral migration of SCs and their accumulation at the ventral aspects of PCV (Figure S13A and S13B). By 52 hpf, despite failure of CVP development in tnnt2a morphants, no changes in the ventral migration or abundance of SCs were observed at the ventral ends of PCV (Figure S13C through S13E).…”

Section: Resultsmentioning

confidence: 97%

Mesenchymal Stromal Cells Facilitate Tip Cell Fusion Downstream of BMP-Mediated Venous Angiogenesis—Brief Report

Eisa-Beygi

Kumar

et al. 2023

ATVB

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BACKGROUND: The goal of this study was to identify and characterize cell-cell interactions that facilitate endothelial tip cell fusion downstream of BMP (bone morphogenic protein)-mediated venous plexus formation. METHODS: High resolution and time-lapse imaging of transgenic reporter lines and loss-of-function studies were carried out to study the involvement of mesenchymal stromal cells during venous angiogenesis. RESULTS: BMP-responsive stromal cells facilitate timely and precise fusion of venous tip cells during developmental angiogenesis. CONCLUSIONS: Stromal cells are required for anastomosis of venous tip cells in the embryonic caudal hematopoietic tissue.

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Section: Resultsmentioning

confidence: 97%

Mesenchymal Stromal Cells Facilitate Tip Cell Fusion Downstream of BMP-Mediated Venous Angiogenesis—Brief Report

Eisa-Beygi

Kumar

et al. 2023

ATVB

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“…As noted earlier, the tail vein undergoes extensive remodeling between 24-48 hpf that involves conversion of an ovoid structure into the caudal venous plexus and caudal vein. This remodeling requires blood flow (Goetz et al, 2014; Karthik et al, 2018; Kugler et al, 2021). Thus, experimentally reducing flow during these early development time points causes a failure to remodel, resulting in a single venous structure with a large lumen.…”

Section: Resultsmentioning

confidence: 99%

Alk1/Endoglin dependent increases in vein endothelial cell sizes precipitate arteriovenous malformations

Diwan,

Siekmann

2023

Preprint

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Aberrations in blood vessel diameters can disrupt the hierarchical patterning of the vasculature and cause congenital vascular anomalies, such as arteriovenous malformations (AVMs). Despite the identification of the Bone Morphogenetic Protein (BMP) pathway as a major driver in AVM pathology, we still lack an understanding of the early embryonic events regulating vessel hierarchy and arteriovenous shunt formationin vivo. We therefore studied blood vessel diameter control of the dorsal aorta (DA) and posterior cardinal vein (PCV) in zebrafish embryos. Our findings reveal that increases in blood flow during embryonic development result in increases in arterial endothelial cell (EC) sizes, ultimately enlarging DA diameters. By contrast, anterior regions of the PCV did not respond to changes in blood flow, while caudal regions, close to the artery-vein junction, responded to changes in flow like the DA, but to a lesser extent. To unravel the mechanisms underlying the reduced response of PCV ECs to flow, we studied zebrafish embryos mutant for the BMP pathway componentsendoglinandalk1. Through the generation of genetic mosaics, we discovered that both Endoglin and Alk1 were required cell autonomously in PCV cells to restrict EC sizes and thereby limit venous diameter increases in response to flow. We further revealed that initial increases in the diameter of the caudal PCV secondarily led to increased DA diameters and cell sizes. Therefore, Alk1/Endoglin signaling prevents vein ECs from behaving like arterial ECs. This differential response of arterial and venous EC cells to increases in flow is necessary to prevent the development of AVMs. This study thus offers insights into the spatiotemporal regulation of vessel hierarchy during early development and identifies changes in EC shapes as an important contributor in determining blood vessel diameters. Failure in this mechanism underlies the vein-specific initiation of AVMs in vertebrate models of HHT.

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“…This challenge also applies to mice embryos. ( 3 ) The circulation deficiency of sih mutant fish is an extreme condition with potential secondary effects[183, 184]. However, as demonstrated by the gata1a mutants, reduced circulatory shear stress induces qualitatively similar effects on DA caliber.…”

Section: Discussionmentioning

confidence: 99%

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

He,

Blazeski,

Nilanthi

et al. 2024

Preprint

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The cardiovascular system generates and responds to mechanical forces. The heartbeat pumps blood through a network of vascular tubes, which adjust their caliber in response to the hemodynamic environment. However, how endothelial cells in the developing vascular system integrate inputs from circulatory forces into signaling pathways to define vessel caliber is poorly understood. Using vertebrate embryos and in vitro-assembled microvascular networks of human endothelial cells as models, flow and genetic manipulations, and custom software, we reveal that Plexin-D1, an endothelial Semaphorin receptor critical for angiogenic guidance, employs its mechanosensing activity to serve as a crucial positive regulator of the Dorsal Aorta's (DA) caliber. We also uncover that the flow-responsive transcription factor KLF2 acts as a paramount mechanosensitive effector of Plexin-D1 that enlarges endothelial cells to widen the vessel. These findings illuminate the molecular and cellular mechanisms orchestrating the interplay between cardiovascular development and hemodynamic forces.

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The effect of absent blood flow on the zebrafish cerebral and trunk vasculature

Cited by 13 publications

References 79 publications

Mesenchymal Stromal Cells Facilitate Tip Cell Fusion Downstream of BMP-Mediated Venous Angiogenesis—Brief Report

Mesenchymal Stromal Cells Facilitate Tip Cell Fusion Downstream of BMP-Mediated Venous Angiogenesis—Brief Report

Alk1/Endoglin dependent increases in vein endothelial cell sizes precipitate arteriovenous malformations

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

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