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Greysson-Wong, J.

Publications and source records attributed to Greysson-Wong, J..

2 recordsLinked to original sources

Vessel Metrics: A python based software tool for automated analysis of vascular structure in confocal imaging

Images contain a wealth of information that is often under analyzed in biological studies. Developmental models of vascular disease are a powerful way to quantify developmentally regulated vessel phenotypes to identify the roots of the disease process. We present vessel Metrics, a software tool specifically designed to analyze developmental vascular microscopy images that will expedite the analysis of vascular images and provide consistency between research groups. We developed a segmentation algorithm that robustly quantifies different image types, developmental stages, organisms, and disease models at a similar accuracy level to a human observer. We validate the algorithm on confocal, lightsheet, and two photon microscopy data in zebrafish. The tool accurately segments data taken by multiple scientists on varying microscopes. We validate vascular parameters such as vessel density, network length, and diameter, across developmental stages, genetic mutations, and drug treatments, and show a favorable comparison to other freely available software tools. Vessel Metrics reduces the time to analyze experimental results, improves repeatability within and between institutions, and expands the percentage of a given vascular network analyzable in experiments. Summary statementVessel Metrics is an automated software tool designed to standardize and streamline the analysis of vascular microscopy images.

developmental biology↗

Venous activation of MEK/ERK drives development of arteriovenous malformation and blood 2 flow anomalies with loss of Rasa1

Vascular malformations develop when growth pathway signaling goes awry in the endothelial cells lining blood vessels. Arteriovenous malformations (AVMs) arise where arteries and veins abnormally connect in patients with loss of RASA1, a Ras GTPase activating protein, and, as we show here, in zebrafish rasa1 mutants. Mutant fish develop massively enlarged vessels at the connection between artery and vein in the tail vascular plexus. These AVMs progressively enlarge and become filled with slow-flowing blood and have a greater drop in pulsatility from the artery to the vein. Expression of the flow responsive transcription factor klf2a is diminished in rasa1 mutants, suggesting changes in flow velocity and pattern contribute to the progression of vessel malformations. Migration of endothelial cells is not affected in rasa1 mutants, nor is cell death or proliferation. Early developmental artery-vein patterning is also normal in rasa1 mutants, but we find that MEK/ERK signaling is ectopically activated in the vein as compared to high arterial activation seen in wildtype animals. MEK/ERK signaling inhibition prevents AVM development of rasa1 mutants, demonstrating venous MEK/ERK drives the initiation of rasa1 AVMs. Thus, rasa1 mutants show overactivation of MEK/ERK signaling causes AVM formation, altered blood flow and downstream flow responsive signaling. SummaryThe zebrafish model of RASA1 capillary malformation and arteriovenous malformation (CM-AVM1) develops cavernous vascular malformations driven by ectopic MEK/ERK signaling in the vein, disrupting flow and downstream mechanosensitive signaling.

developmental biology↗