Abstract Vertebrate Delta/Notch signaling involves multiple ligands, receptors and transcription factors. Delta endocytosis – a critical event for Notch activation – is however essentially controlled by the E3 Ubiquitin ligase Mindbomb1 (Mib1). Mib1 inactivation is therefore often used to inhibit Notch signaling. However, recent findings indicate that Mib1 function extends beyond the Notch pathway. We report a novel Notch-independent role of Mib1 in zebrafish gastrulation.