Live Cell Imaging – Vascular defects of DYRK1A knockouts are ameliorated by modulating calcium signaling in zebrafish. Disease models & mechanisms

time22/03/04
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Abstract

DYRK1A is a major causative gene in Down syndrome (DS). Reduced incidence of solid tumors such as neuroblastoma in DS patients and increased vascular anomalies in DS fetuses suggest a potential role of DYRK1A in angiogenic processes, but in vivo evidence is still scarce.

Here, researchers used zebrafish dyrk1aa mutant embryos to understand DYRK1A function in cerebral vasculature formation. Zebrafish dyrk1aa mutants exhibited cerebral hemorrhage and defects in angiogenesis of central arteries in the developing hindbrain. Together, results suggest that DYRK1A plays an essential role in angiogenesis and in maintenance of the developing cerebral vasculature via regulation of calcium signaling, which may have therapeutic potential for DYRK1A-related vascular diseases.

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Fig1 dyrk1ab is expressed in the developing brain region. By WISH (whole mount in situhybridization), dyrk1ab was expressed in the forebrain (black arrowheads, a-f; black brackets, g-l), the midbrain(gray arrowheads, a-f; gray brackets, g-l), the hindbrain (blue arrowheads, a-f; blue brackets, g-l) at 24, 48 and 72 hpf and the spinal cord (orange arrowheads, a and b) at 24 hpf. It was also detected in the heart (asterisks, d, f, j and l) and in the retina (red arrows, i-l) at 48 and 72 hpf. (m and n) Sectioned images of WISH embryos showed the expression of dyrk1ab in the tectum (green arrows) and the retina (red arrows) at 48 hpf and 72 hpf.

Analysis of imaging technology

The experiment needs to image the mutant gene of zebrafish, which requires the camera to have good sensitivity to reduce exposure time and a large enough field of view to collect more data for the experiment. The readout noise of Dhyana 400DC camera is only 2 electrons. The stable cooling effect of -10℃ can significantly control dark current and improve signal-to-noise ratio. 1.2 "provides a larger field of view for the microscope observer, reduces the number of images and acquisition time, and provides excellent imaging support for research.

Reference source

Cho, H. J., Lee, J. G., Kim, J. H., Kim, S. Y., Huh, Y. H., Kim, H. J., Lee, K. S., Yu, K., & Lee, J. S. (2019). Vascular defects of DYRK1A knockouts are ameliorated by modulating calcium signaling in zebrafish. Disease models & mechanisms, 12(5), dmm037044. https://doi.org/10.1242/dmm.037044

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