Raw images from: Genetic inactivation of the β1 adrenergic receptor prevents Cerebral Cavernous Malformations in zebrafish

Propranolol reduces experimental murine Cerebral Cavernous Malformations (CCMs) and prevents embryonic caudal venous plexus (CVP) lesions in zebrafish that follow mosaic inactivation of ccm2(Li et al., 2021). Because morpholino silencing of the β1 adrenergic receptor (adrb1) prevents the embryonic CVP lesion, we proposed that adrb1 plays a role in CCM pathogenesis. Here we report that adrb1-/- zebrafish exhibited 86% fewer CVP lesions and 87% reduction of CCM lesion volume relative to wild type brood mates at 2dpf and 8-10 weeks stage, respectively. Treatment with metoprolol, a β1 selective antagonist, yielded a similar reduction in CCM lesion volume. Adrb1-/- zebrafish embryos exhibited reduced heart rate and contractility and reduced CVP blood flow. Similarly, slowing the heart and eliminating the blood flow in CVP by administration of 2,3-BDM suppressed the CVP lesion. In sum, our findings provide genetic and pharmacological evidence that the therapeutic effect of propranolol on CCM ..., , , # Raw images from: Genetic inactivation of the β1 adrenergic receptor prevents Cerebral Cavernous Malformations in zebrafish

[https://doi.org/10.5061/dryad.dz08kps7n](https://doi.org/10.5061/dryad.dz08kps7n)

## Description of the data and file structure

These images (CZI file) are from Zeiss LSM 880 Confocal with Airyscan, and can be viewed with ZEN or ImageJ.

Figure 1: Following *ccm2* CRISPR injection, representative confocal images of 2 dpf Tg(fli1:EGFP) embryos illustrate that wild-type embryos (file “WT CCM2 CRISPR 2DPF-4_Airyscan Processing”) exhibit CVP dilation, whereas *adrb1⁻/⁻* embryos (file “ADRB1 NULL CCM2 CRISPR 2DPF-2_Airyscan Processing”) are resistant to this defect.

Figure 4: Adrb1 signaling does not affect *klf2a* expression in *ccm2* CRISPR embryos. Tg(klf2a:H2b-EGFP; kdrl:mCherry) embryos were injected, and nuclear EGFP signal in mCherry-labeled vascular endothelial cells was recorded using confocal microscopy. Representative images from each group are shown.
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