TY - JOUR TI - The E3 ubiquitin ligase mindbomb1 controls planar cell polarity-dependent convergent extension movements during zebrafish gastrulation AU - Saraswathy, Vishnu Muraleedharan AU - Kurup, Akshai Janardhana AU - Sharma, Priyanka AU - Polès, Sophie AU - Poulain, Morgane AU - Fürthauer, Maximilian A2 - Chitnis, Ajay A2 - Stainier, Didier YR A2 - Chitnis, Ajay VL - 11 PY - 2022 DA - 2022/02/10 SP - e71928 C1 - eLife 2022;11:e71928 DO - 10.7554/eLife.71928 UR - https://doi.org/10.7554/eLife.71928 AB - 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. mib1 null mutants and morphants display impaired Convergence Extension (CE) movements. Comparison of different mib1 mutants and functional rescue experiments indicate that Mib1 controls CE independently of Notch. Mib1-dependent CE defects can be rescued using the Planar Cell Polarity (PCP) downstream mediator RhoA, or enhanced through knock-down of the PCP ligand Wnt5b. Mib1 regulates CE through its RING Finger domains that have been implicated in substrate ubiquitination, suggesting that Mib1 may control PCP protein trafficking. Accordingly, we show that Mib1 controls the endocytosis of the PCP component Ryk and that Ryk internalization is required for CE. Numerous morphogenetic processes involve both Notch and PCP signaling. Our observation that during zebrafish gastrulation Mib1 exerts a Notch-independent control of PCP-dependent CE movements suggest that Mib1 loss-of-function phenotypes should be cautiously interpreted depending on the biological context. KW - Mindbomb1 KW - PCP KW - zebrafish KW - Convergent Extension KW - Ryk JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -