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Switch in FGF signalling initiates glial differentiation in the Drosophila eye


The formation of a complex nervous system requires the intricate interaction of neurons and glial cells. Glial cells generally migrate over long distances before they initiate their differentiation, which leads to wrapping and insulation of axonal processes1,2. The molecular pathways coordinating the switch from glial migration to glial differentiation are largely unknown3. Here we demonstrate that, within the Drosophila eye imaginal disc, fibroblast growth factor (FGF) signalling coordinates glial proliferation, migration and subsequent axonal wrapping. Glial differentiation in the Drosophila eye disc requires a succession from glia–glia interaction to glia–neuron interaction4. The neuronal component of the fly eye develops in the peripheral nervous system within the eye–antennal imaginal disc, whereas glial cells originate from a pool of central-nervous-system-derived progenitors and migrate onto the eye imaginal disc5,6,7,8. Initially, glial-derived Pyramus, an FGF8-like ligand, modulates glial cell number and motility. A switch to neuronally expressed Thisbe, a second FGF8-like ligand, then induces glial differentiation. This switch is accompanied by an alteration in the intracellular signalling pathway through which the FGF receptor channels information into the cell. Our findings reveal how a switch from glia–glia interactions to glia–neuron interactions can trigger formation of glial membrane around axonal trajectories. These results disclose an evolutionarily conserved control mechanism of axonal wrapping2, indicating that Drosophila might serve as a model to understand glial disorders in humans.

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Figure 1: The role of Htl during glial development in the eye disc.
Figure 2: Pyr directs glial proliferation and migration.
Figure 3: Ths controls glial differentiation.
Figure 4: FGF signalling in migrating and differentiating glial cells.

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We thank A. Müller for providing flies and advice, M. Leptin, M. Freeman, the Bloomington stock centre and the Vienna Drosophila RNAi Center (VDRC) for sending flies and antibodies, H. Aberle, S. Bogdan, T. Hummel, E. Raz, M. Silies and R. Stephan for discussions. The work was funded through grants of the Deutsche Forschungsgemeinschaft.

Author Contributions S.R.F. performed the analysis of FGFR function during eye disc glial development (MARCM analysis, RNA interference, gain of function analysis and confocal studies), generated the antibodies and devised the genetic crosses. D.E. conducted the electron microscopic analysis and determined the phenotype of pyramus and thisbe mutants. Y.Y.-A. performed the cell-type-specific mRNA isolation, I.S. conducted the pnt MARCM analysis and A.A. contributed to the statistical analysis. C.K. contributed ideas, coordinated the work and wrote the manuscript.

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Correspondence to Christian Klämbt.

Supplementary information

Supplementary Information

This file contains Supplementary Figures S1-S8 with Legends and Legends for Supplementary Movies 1 and 2. (PDF 5827 kb)

Supplementary Movie 1

This movie file shows Pyramus inducing glial motility (see file s1 for full Legend). (MOV 8405 kb)

Supplementary Movie 2

This movie file shows Pyramus acting as a permissive cue for glial migration (see file s1 for full Legend). (MOV 8667 kb)

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Franzdóttir, S., Engelen, D., Yuva-Aydemir, Y. et al. Switch in FGF signalling initiates glial differentiation in the Drosophila eye. Nature 460, 758–761 (2009).

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