Our own work on alveolar rhabdomyosarcoma, a clinically aggressive tumor driven by oncogenic PAX3–FOXO1 fusion proteins, leveraged developmental assays in zebrafish embryos and adult tumor models to identify HES3 as a cooperating oncogene that impairs muscle differentiation and contributes to poor clinical outcomes (Kendall et al., 2018). The gene discussed is HES3; the disease is neoplasm.