8/9. Strikingly, EWSR1::FLI1-expressing cells induced ectopic fin formation by locally activating Fgfr and Hox signaling, eventually giving rise to tumors. This suggests that pre-tumor cells hijack developmental programs to establish a local signaling environment for tumor initiation.

5/9. Next, we generated a stable zebrafish line with tissue-specific expression of human EWSR1::FLI1 in NCCs. This led to the development of pre-tumor outgrowths and, eventually, massive tumors, demonstrating that the expression of the oncofusion in NCCs is tumorigenic in vivo.

4/9 First, using our mosaic zebrafish model of Ewing sarcoma, we traced EWSR1::FLI1 positive cells in early development and found that lineage, timing, and expression level of the oncofusion are critical. In our model, neural crest cells uniquely tolerated this toxic oncofusion in vivo.

3/9 In this study, we use zebrafish genetic cancer models to investigate the origin of #EwingSarcoma. We show that EWSR1::FLI1 alters embryonic cell fate decisions, reprogramming neural crest cells into a mesoderm-like state that initiates this devastating childhood cancer.

I feel privileged to be supported by Silken Twine Charity in attending the AACR Annual Meeting 2025. Happy to be here! Thanks for your support! @amatrudalab.bsky.social @theaacr.bsky.social

I'm really excited for the chance to visit Caltech this week and share our research on the Ewing sarcoma cell of origin. #zebrafish #ewingsarcoma #development

Happy Valentine’s Day to my favorite creatures🤍 #zebrafish