The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling
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Publication Date
2017-01-09Journal Title
Developmental Cell
ISSN
1534-5807
Publisher
Elsevier
Volume
40
Issue
1
Pages
67-80
Language
English
Type
Article
This Version
VoR
Metadata
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Martins, T., Meghini, F., Florio, F., & Kimata, Y. (2017). The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling. Developmental Cell, 40 (1), 67-80. https://doi.org/10.1016/j.devcel.2016.12.005
Abstract
The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing $\textit{Drosophila}$eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, $\textit{Drosophila}$ Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways.
Keywords
APC/C, proteolysis, wingless, Wnt, Drosophila, Nek2, eye development, Dpp, differentiation, fate specification
Sponsorship
T.M. and F.M. were partly supported by a CRUK Fellowship to Y.K. T.M. thanks the European Commission for a Marie Curie fellowship.
Funder references
Cancer Research UK (12874)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (655297)
Identifiers
External DOI: https://doi.org/10.1016/j.devcel.2016.12.005
This record's URL: https://www.repository.cam.ac.uk/handle/1810/262437
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International