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iScience. 2019 Jul 26;17:49-66. doi: 10.1016/j.isci.2019.06.021. Epub 2019 Jun 18.

Experimental and Theoretical Evidence for Bidirectional Signaling via Core Planar Polarity Protein Complexes in Drosophila.

Author information

1
Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
2
Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. Electronic address: d.strutt@sheffield.ac.uk.
3
School of Mathematics and Statistics, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH, UK; Bateson Centre, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. Electronic address: a.g.fletcher@sheffield.ac.uk.

Abstract

In developing tissues, sheets of cells become planar polarized, enabling coordination of cell behaviors. It has been suggested that "signaling" of polarity information between cells may occur either bidirectionally or monodirectionally between the molecules Frizzled (Fz) and Van Gogh (Vang). Using computational modeling we find that both bidirectional and monodirectional signaling models reproduce known non-autonomous phenotypes derived from patches of mutant tissue of key molecules but predict different phenotypes from double mutant tissue, which have previously given conflicting experimental results. Furthermore, we re-examine experimental phenotypes in the Drosophila wing, concluding that signaling is most likely bidirectional. Our modeling suggests that bidirectional signaling can be mediated either indirectly via bidirectional feedbacks between asymmetric intercellular protein complexes or directly via different affinities for protein binding in intercellular complexes, suggesting future avenues for investigation. Our findings offer insight into mechanisms of juxtacrine cell signaling and how tissue-scale properties emerge from individual cell behaviors.

KEYWORDS:

Biological Sciences; Developmental Biology; In Silico Biology

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