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Discs large 1 controls daughter-cell polarity after cytokinesis in vertebrate morphogenesis

Li, Yuwei and Junge, Jason A. and Arnesano, Cosimo and Gross, Garrett G. and Miner, Jeffrey H. and Moats, Rex and Roberts, Richard W. and Arnold, Don B. and Fraser, Scott E. (2018) Discs large 1 controls daughter-cell polarity after cytokinesis in vertebrate morphogenesis. Proceedings of the National Academy of Sciences of the United States of America, 115 (46). E10859-E10868. ISSN 0027-8424. PMCID PMC6243286. doi:10.1073/pnas.1713959115.

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Vertebrate embryogenesis and organogenesis are driven by cell biological processes, ranging from mitosis and migration to changes in cell size and polarity, but their control and causal relationships are not fully defined. Here, we use the developing limb skeleton to better define the relationships between mitosis and cell polarity. We combine protein-tagging and -perturbation reagents with advanced in vivo imaging to assess the role of Discs large 1 (Dlg1), a membrane-associated scaffolding protein, in mediating the spatiotemporal relationship between cytokinesis and cell polarity. Our results reveal that Dlg1 is enriched at the midbody during cytokinesis and that its multimerization is essential for the normal polarity of daughter cells. Defects in this process alter tissue dimensions without impacting other cellular processes. Our results extend the conventional view that division orientation is established at metaphase and anaphase and suggest that multiple mechanisms act at distinct phases of the cell cycle to transmit cell polarity. The approach employed can be used in other systems, as it offers a robust means to follow and to eliminate protein function and extends the Phasor approach for studying in vivo protein interactions by frequency-domain fluorescence lifetime imaging microscopy of Förster resonance energy transfer (FLIM-FRET) to organotypic explant culture.

Item Type:Article
Related URLs:
URLURL TypeDescription Information CentralArticle
Li, Yuwei0000-0001-7753-4869
Miner, Jeffrey H.0000-0002-1510-8714
Roberts, Richard W.0000-0002-8587-5097
Fraser, Scott E.0000-0002-5377-0223
Additional Information:© 2018 the Author(s). Published under the PNAS license. Edited by Richard M. Harland, University of California, Berkeley, CA, and approved September 26, 2018 (received for review August 31, 2017). We thank Prof. Francesca Mariani for her critical reading of the manuscript, Prof. Cheng-Ming Chuong for sharing equipment, Ang Li for statistical analyses and sharing reagents, Francesco Cutrale for helpful discussions and editing, Prof. Rich Roberts for the mRNA display without which FingRs would not exist, and Annie Moradian and Michael Sweredoski of the Proteome Exploration Laboratory at the California Institute of Technology for services, troubleshooting, and experimental advice regarding mass spectroscopy. This study was supported by the University of Southern California Translational Imaging Center. Y.L. and J.A.J. contributed equally to this work. Author contributions: Y.L., J.A.J., and S.E.F. designed research; Y.L., J.A.J., and C.A. performed research; J.H.M. provided all mouse tissues; Y.L., J.A.J., C.A., G.G.G., J.H.M., R.M., R.W.R., D.B.A., and S.E.F. contributed new reagents/analytic tools; Y.L., J.A.J., C.A., and S.E.F. analyzed data; and Y.L., J.A.J., C.A., D.B.A., and S.E.F. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at
Funding AgencyGrant Number
University of Southern CaliforniaUNSPECIFIED
Subject Keywords:intrabody; FingR; cell polarity; DLGE3; bone morphogenesis
Issue or Number:46
PubMed Central ID:PMC6243286
Record Number:CaltechAUTHORS:20181030-105012922
Persistent URL:
Official Citation:Discs large 1 controls daughter-cell polarity after cytokinesis in vertebrate morphogenesis. Yuwei Li, Jason A. Junge, Cosimo Arnesano, Garrett G. Gross, Jeffrey H. Miner, Rex Moats, Richard W. Roberts, Don B. Arnold, Scott E. Fraser. Proceedings of the National Academy of Sciences Nov 2018, 115 (46) E10859-E10868; DOI: 10.1073/pnas.1713959115
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90493
Deposited By: George Porter
Deposited On:30 Oct 2018 18:18
Last Modified:16 Nov 2021 03:33

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