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Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway

Nature Cell Biology volume 8, pages 55–63 (2006)Cite this article

An Erratum to this article was published on 01 February 2006

Abstract

An important step in retinal development is the positioning of progenitors within the eye field where they receive the local environmental signals that will direct their ultimate fate1. Recent evidence indicates that ephrinB1 functions in retinal progenitor movement, but the signalling pathway is unclear. We present evidence that ephrinB1 signals through its intracellular domain to control retinal progenitor movement into the eye field by interacting with Xenopus Dishevelled (Xdsh), and by using the planar cell polarity (PCP) pathway. Blocking Xdsh translation prevents retinal progeny from entering the eye field, similarly to the morpholino-mediated loss of ephrinB1 (ref. 2). Overexpression of Xdsh can rescue the phenotype induced by loss of ephrinB1, and this rescue (as well as a physical association between Xdsh and ephrinB1) is completely dependent on the DEP (Dishevelled, Egl-10, Pleckstrin) domain of Xdsh. Similar gain- and loss-of-function experiments suggest that Xdsh associates with ephrinB1 and mediates ephrinB1 signalling through downstream members of the PCP pathway during eye field formation.

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Figure 1: Xdsh is expressed in the eye field, interacts with ephrinB1 through the DEP (Dishevelled, Egl-10, Pleckstrin) domain, and is essential for eye-field formation.
Figure 2: The DEP domain of Xdsh is necessary for ephrinB1-driven movement of non-retinal progenitor cells into the retina.
Figure 3: PKCδ is an essential downstream mediator for ephrinB1–Xdsh-driven cell movement.
Figure 4: Inhibition of the ephrinB1–Xdsh–PKCδ pathway represses retinal fate and expands ventral neural fate.
Figure 5: Downstream members of the non-canonical Wnt–PCP pathway are critical for ephrinB1–Xdsh–PKCδ-driven population of the retina.

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Acknowledgements

We thank R. Moon for Xdsh and Xwnt5a (RPA) constructs; N. Kinoshita for PKCδ1, PKCδ2 constructs; S. Sokol for DN Tcf3 construct; L. Heasley for MKK7–JNK1 fusion construct; T. Yamaguchi for Daam1 MO; J. Gautier for tPARP construct; R. Winklbauer for Xfz7, ΔC Xfz7 constructs; K. Itoh and J. Miller for Xdsh–GFP constructs; P. McCrea for Xwnt11, DN Xwnt11 constructs and D. Morrison for cdc25c and anti-polyoma antibody. We also thank J. Acharya, S. Sharan, and M. Fortini for helpful discussions and critical reading of this manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, and NIH EY10096.

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Authors and Affiliations

  1. Laboratory of Protein Dynamics and Signaling, National Cancer Institute-Frederick, Frederick, 21702, MD, USA

    Hyun-Shik Lee, Yong-Sik Bong, Kathleen Soria & Ira O. Daar

  2. Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, 84132, UT, USA

    Kathryn B. Moore

  3. Department of Anatomy and Cell Biology, The George Washington University Medical Center, Washington, 20037, DC, USA

    Sally A. Moody

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Correspondence to Ira O. Daar.

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Lee, HS., Bong, YS., Moore, K. et al. Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway. Nat Cell Biol 8, 55–63 (2006). https://doi.org/10.1038/ncb1344

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