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.