Homeostasis of the Drosophila adult retina by Actin-Capping Protein and the Hippo pathway

Abstract

The conserved Hippo signalling pathway regulates multiple cellular events, including tissue growth, cell fate decision and neuronal homeostasis. While the core Hippo kinase module appears to mediate all the effects of the pathway, various upstream inputs have been identified depending on tissue context. We have recently shown that, in the Drosophila wing imaginal disc, actin-Capping Protein and Hippo pathway activities inhibit F-actin accumulation. In turn, the reduction in F-actin sustains Hpo pathway activity, preventing Yorkie nuclear translocation and the upregulation of proliferation and survival genes. Here, we investigate the role of Capping Protein in growth-unrelated events controlled by the Hippo pathway. We provide evidence that loss of Capping Protein induces degeneration of the adult Drosophila retina through misregulation of the Hippo pathway. We propose a model by which F-actin dynamics might be involved in all processes that require the activity of the core Hippo kinase module. 

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Acknowledgments

We thank D.J. Pan, R.G. Fehon, the Bloomington Drosophila Stock Center, the Drosophila Genomics Resource Center, the Vienna Drosophila Research Center (VDRC) and the National Institute of Genetics (NIG) for fly stocks. The manuscript was improved by the critical comments of Beatriz García Fernández and Barbara Jezowska. This work was supported by grants (PTDC/SAU-OBD/73191/2006 and PTDC/BIA-BCM/71674/2006) from Fundação para a Ciência e Tecnologia (FCT). C.B.P. was the recipient of fellowships from FCT (SFRH/BPD/46983/2008), and NEI grant R01EY013167 to F.P.

Figures and Tables

Figure 1 Knocking down Capping Protein triggers retinal degeneration through inhibition of Hippo signaling activity. All panels show adult Drosophila retina. The genotypes of the animals are indicated above the panels. ato³⁴⁸ or GMR refers to ato³⁴⁸-Gal4 or GMR-Gal4 driving expression of the indicated transgenes (UAS-cpb⁴⁵⁶⁶⁸, UAS-cpa-IR^C10, UAS-yki^4005R-2, UAS-hpo^M11.1 or UAS-ex) and either wild-type for the hpo gene (A) or heterozygote for the hpo^42–47 allele (B and C).

Figure 2 Model for the role of F-actin in Hippo signaling activity. The core kinase module of the Hpo pathway regulates multiple outputs, including tissue growth, neuronal homeostasis and autophagy. Hpo-dependent tissue growth is mediated through inhibition of Yki by a phosphorylation-dependent and independent mechanisms. The neuroprotective effect of Hpo signaling also required Yki inhibition, independent of its phosphorylation by Wts. In contrast, Yki is not involved in Hpo-dependent autophagy. The core kinase complex is regulated by multiple inputs, including Fat and Ex. The interplay between Hpo signaling activity and F-actin dynamics may be a general requirement in Hpo signaling.

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