ZFIN Image: Phelps et al., 2022, Fig. 1

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Fig. 1

Mitfa loss accelerates GNAQ^Q209L-driven tumorigenesis, and resulting tumors stain negatively for hyperactive ERK; Q, Tg(mitfa:GNAQ^Q209L); p, tp53^M214K/M214K; m+, mitfa^+/+; m−, mitfa^−/−; p^+/−, tp53^+/M214K. (A) Kaplan–Meier curves for the indicated genotypes show that overall survival of Tg(mitfa:GNAQ^Q209L)-expressing zebrafish was significantly decreased by mitfa deficiency (P < 0.0001, determined by log-rank test). The pm+ and pm− zebrafish develop MPNSTs, while Qpm+ and Qpm− zebrafish develop UMs and, less frequently, MPNSTs. (B) A representative image, with tumor outlined by dotted line, shows the typical unpigmented UM tumor phenotype of Qpm− zebrafish. (C) Kaplan–Meier curves show that mitfa^−/− also cooperates with GNAQ^Q209L to decrease overall survival in a tp53-WT background. The Qpm+ and Qpm− curves from A are included for comparison. (D) Kaplan–Meier curves showing that Qp^+/−m− zebrafish have significantly reduced survival compared to Qp^+/−m+ counterparts (P < 0.0001, determined by log-rank test) as well as a reduced reliance on tp53 LOH, as determined by DNA sequencing of the mutation-bearing tp53 exon of excised tumors. (E) Representative images (n ≥ 3 for each stain and genotype) of hematoxylin and eosin (H&E) and IHC for YAP, ERK1/2, and phospho-ERK1/2 (pERK; active) for Qpm+ and Qpm− tumors. YAP activation was detected through nuclear localization.

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Acknowledgments

This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Proc. Natl. Acad. Sci. USA