Abstract
Understanding how epithelial polarity is established and regulated during tissue morphogenesis is a major issue. Here, we identify a regulatory mechanism important for mesoderm invagination, germ-band extension and transepithelial migration in the Drosophila melanogaster embryo. This mechanism involves the inhibition of the conserved E3 ubiquitin ligase Neuralized by proteins of the Bearded family. First, Bearded mutant embryos exhibited a loss of epithelial polarity associated with an early loss of the apical domain. Bearded regulated epithelial polarity by antagonizing neuralized. Second, repression of Bearded gene expression by Snail was required for the Snail-dependent disassembly of adherens junctions in the mesoderm. Third, neuralized was strictly required to promote the downregulation of the apical domain in the midgut epithelium and to facilitate the transepithelial migration of primordial germ cells across this epithelium. This function of Neuralized was independent of its known role in Notch signalling. Thus, Neuralized has two distinct functions in epithelial cell polarity and Notch signalling.
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Acknowledgements
We thank M. Biggin (Lawrence Berkeley National Laboratory, Berkeley, USA), P. Bryant (University of California Irvine, Irvine, California, USA), K. Choi (Baylor College of Medicine, Houston, Texas, USA), Y-N. Jan (University of California San Francisco, San Francisco, California, USA), D. Kiehart (Duke University, Durham, North Carolina, USA), J. Knoblich (Institute of Molecular Biotechnology, Austria, Vienna), P. Lasko (McGill University, Montreal, Quebec, Canada), M. Leptin (University of Koln, Koln, Germany), A. Martinez-Arias (University of Cambridge, Cambridge, UK), N. Perrimon (Harvard University, Boston, USA), A. Preiss (University of Hohenheim, Hohenheim, Germany), M. Rand, (University of Vermont, Burlington, Vermont, USA), J. Skeath (Washington University, Saint Louis, Missouri, USA), U. Tepass (University of Toronto, Toronto, Canada), E. Wieschaus (Princeton University, Princeton, New Jersey, USA) and A. Wodarz (University of Góttingen, Góttingen, Germany) the Bloomington Drosophila Stock Center, the Developmental Studies Hybridoma Bank and Flybase for flies, antibodies and other resources. We thank S. Guadagnini for the scanning electron microscopy. We are very grateful to L. Couturier for her help in the analysis of midgut polarity. We thank V. Mayau for technical help and A. Bardin, T. Lecuit, M. Leptin and all laboratory members for discussion and critical reading. This work was financially supported by the CNRS, Institut Pasteur, ANR (08-BLAN-0235) and FRM (DEQ20100318284). S.C. received fellowships from the MENRT and the ARC.
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S.C. performed all of the experiments. F.S. and S.C. analysed the data and wrote the paper.
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Chanet, S., Schweisguth, F. Regulation of epithelial polarity by the E3 ubiquitin ligase Neuralized and the Bearded inhibitors in Drosophila. Nat Cell Biol 14, 467–476 (2012). https://doi.org/10.1038/ncb2481
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DOI: https://doi.org/10.1038/ncb2481
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