The E3 Ubiquitin Ligase Mindbomb1 controls planar cell polarity-dependent convergent extension movements during zebrafish gastrulation
- Université Côte d'Azur, CNRS, Inserm, iBV, France
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. 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.
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All data generated or analysed during this study are included in the manuscript.
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Author details
Maximilian Fürthauer
Funding
Fondation ARC pour la Recherche sur le Cancer (PJA20181208167)
- Maximilian Fürthauer
Agence Nationale de la Recherche (ANR-17-CE13-0024-02)
- Maximilian Fürthauer
Agence Nationale de la Recherche (ANR-11-LABX-0028-01)
- Vishnu Muraleedharan Saraswathy
Ligue Contre le Cancer (IP/SC-17131)
- Akshai Janardhana Kurup
Fondation pour la Recherche Médicale (FDT20140930987)
- Priyanka Sharma
Human Frontier Science Program (CDA00036/2010)
- Maximilian Fürthauer
Centre National de la Recherche Scientifique (ATIP2010)
- Maximilian Fürthauer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were performed in the iBV Zebrafish facility (authorization #B-06-088-17) in accordance with the guidelines of the ethics committee Ciepal Azur and the iBV animal welfare committee (project authorizations NCE/2013-92, 19944-2019031818528380).
Copyright
© 2022, Saraswathy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The E3 Ubiquitin Ligase Mindbomb1 controls planar cell polarity-dependent convergent extension movements during zebrafish gastrulation
eLife 11:e71928.
https://doi.org/10.7554/eLife.71928
