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APC/CFzr/Cdh1-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS

Nature Neuroscience volume 13, pages 1357–1364 (2010)Cite this article

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Abstract

Interactions between neurons and glia are a key feature during the assembly of the nervous system. During development, glial cells often follow extending axons, implying that axonal outgrowth and glial migration are precisely coordinated. We found that the anaphase-promoting complex/cyclosome (APC/C) co-activator fizzy-related/Cdh1 (Fzr/Cdh1) is involved in the non-autonomous control of peripheral glial migration in postmitotic Drosophila neurons. APC/CFzr/Cdh1 is a cell-cycle regulator that targets proteins that are required for G1 arrest for ubiquitination and subsequent degradation. We found that Fzr/Cdh1 function is mediated by the immunoglobulin superfamily cell adhesion molecule Fasciclin2 (Fas2). In motor neurons Fzr/Cdh1 is crucial for the establishment of a graded axonal distribution of Fas2. Axonal Fas2 interacts homophilically with a glial isoform of Fas2. Glial migration is initiated along axonal segments that have low levels of Fas2 but stalls in axonal domains with high levels of Fas2 on their surfaces. This represents a simple mechanism by which a subcellular gradient of adhesiveness can coordinate glial migration with axonal growth.

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Figure 1: Identification of fzr/cdh1 mutants.
Figure 2: Postmitotic Fzr/Cdh1 non-autonomously regulates glial cell migration.
Figure 3: Postmitotic APC/C acts in motor neurons to control glial migration.
Figure 4: Fzr/Chd1 regulates glial cell migration through the homophilic cell adhesion molecule Fas2.
Figure 5: Broad expression of fas2.
Figure 6: Fzr/Cdh1 regulates the graded expression of Fasciclin 2 at the onset of glial migration.
Figure 7: Disruption of the endocytic pathway disrupts glial migration and reduces the graded expression of Fas2.

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Acknowledgements

We thank C. Lehner, J. Raff, B. Altenhein, T. Orr-Weaver, G. Tear, K. Basler, M. Landgraf and A. Nose for flies and antibodies; T. Hummel, E. Raz, A. Püschel and T.R. Clandinin for comments on the manuscript; G. Edenfeld, K. Krukkert, N. Otto, A. Weinbrecht and H. Neuert for help with initial experiments; J. Lipp for help with statistical analysis; and members of the Klämbt lab for support and discussions. This work was supported by a PhD fellowship of the Boehringer Ingelheim Fonds to M.S. and grants of the Deutsche Forschungsgemeinschaft to C.K.

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  1. Marion Silies

    Present address: Present address: Department of Neurobiology, Stanford University, Stanford, California, USA.,

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  1. Institut für Neurobiologie, Universität Münster, Münster, Germany

    Marion Silies & Christian Klämbt

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M.S. conducted the experiments and analysed the data. C.K. contributed ideas. M.S. and C.K. wrote the manuscript.

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Correspondence to Christian Klämbt.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–10 (PDF 6519 kb)

Supplementary Movie 1

Wild type embryo carrying two repoGal4 and two UAS-GFPstinger transgenes. (MOV 1353 kb)

Supplementary Movie 2

fzr/cdh1ie28 mutant type embryo carrying two repoGal4 and two UAS-GFPstinger transgenes. (MOV 3612 kb)

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Silies, M., Klämbt, C. APC/CFzr/Cdh1-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS. Nat Neurosci 13, 1357–1364 (2010). https://doi.org/10.1038/nn.2656

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